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| Publications of Kam W. Leong :chronological alphabetical combined listing:
%% Papers Published
@article{fds215936,
Author = {K.W. Leong},
Title = {Synthetic mast-cell granules as adjuvants to promote and
polarize immunity in lymph nodes},
Year = {2013},
Key = {fds215936}
}
@article{fds215937,
Author = {K.W. Leong},
Title = {Tuning Physical Properties of Nanocomplexes through
Microfluidics-Assisted Confinement},
Year = {2013},
Key = {fds215937}
}
@article{fds215938,
Author = {K.W. Leong},
Title = {Nucleic acid scavengers inhibit thrombosis without
increasing bleeding},
Year = {2013},
Key = {fds215938}
}
@article{fds215939,
Author = {K.W. Leong},
Title = {Nanotopography as modulator of human mesenchymal stem cell
function},
Year = {2013},
Key = {fds215939}
}
@article{fds215940,
Author = {K.W. Leong},
Title = {Efficacy of engineered FVIII-producing skeletal muscle
enhanced by growth factor-releasing co-axial electrospun
fibers},
Year = {2013},
Key = {fds215940}
}
@article{Article,
Author = {Zhao, F. and Veldhuis, J. J. and Duan, Y. J. and Yang, Y. and Christoforou, N. and Ma, T. and Leong, K.
W.},
Title = {Low Oxygen Tension and Synthetic Nanogratings Improve the
Uniformity and Stemness of Human Mesenchymal Stem Cell
Layer},
Journal = {Molecular Therapy},
Volume = {18},
Number = {5},
Pages = {1010-1018},
Year = {2010},
Keywords = {marrow stromal cells smooth-muscle-cells
extracellular-matrix osteogenic differentiation
gene-expression hypoxia tissues organization myocardium
infarction},
Abstract = {A free-standing, robust cell sheet comprising aligned human
mesenchymal stem cells (hMSCs) offers many interesting
opportunities for tissue reconstruction. As a first step
toward this goal, a confluent, uniform hMSC layer with a
high degree of alignment and stemness maintenance needs to
be created. Hypothesizing that topographical cue and a
physiologically relevant low-oxygen condition could promote
the formation of such an hMSC layer, we studied the culture
of hMSCs on synthetic nanogratings (350 nm width and 700 nm
pitch) and either under 2 or 20% O-2. Culturing hMSCs on the
nanogratings highly aligned the cells, but it tended to
create patchy layers and accentuate the hMSC
differentiation. The 2% O-2 improved the alignment and
uniformity of hMSCs, and reduced their differentiation. Over
a 14-day culture period, hMSCs in 2% O-2 showed uniform
connexon distribution, secreted abundant extracellular
matrix (ECM) proteins, and displayed a high progenicity.
After 21-day culture on nanogratings, hMSCs exposed to 2%
O-2 maintained a higher viability and differentiation
capacity. This study established that a 2% O-2 culture
condition could restrict the differentiation of hMSCs
cultured on nanopatterns, thereby setting the foundation to
fabricate a uniformly aligned hMSC sheet for different
regenerative medicine applications.},
Key = {Article}
}
@article{Article,
Author = {Kadiyala, I. and Loo, Y. H. and Roy, K. and Rice, J. and Leong, K. W.},
Title = {Transport of chitosan-DNA nanoparticles in human intestinal
M-cell model versus normal intestinal enterocytes},
Journal = {European Journal of Pharmaceutical Sciences},
Volume = {39},
Number = {1-3},
Pages = {103-109},
Year = {2010},
Keywords = {m-cells chitosan nanoparticles transcytosis nonviral gene
delivery nanomedicine patch m-cells caco-2 cells oral
vaccination gene delivery functional-characteristics drug
transport microparticles murine line permeability},
Abstract = {Oral vaccination is one of the most promising applications
of polymeric nanoparticles. Using two different in vitro
cellular models to partially reproduce the characteristics
of intestinal enterocytes and M-cells, this study
demonstrates that nanoparticle transport through the M-cell
co-culture model is 5-fold that of the intestinal epithelial
monolayer. with at least 80% of the chitosan-DNA
nanoparticles uptaken in the first 30 min. Among the
properties of nanoparticles Studied, ligand decoration has
the most dramatic effect on the transcytosis rate:
transferrin modification enhances transport through both
models by 3- to 5-fold. The stability of the nanoparticles
also affects transport kinetics. Factors which de-stabilize
the nanoparticles, such as low charge (N/P) ratio and
addition of serum, result in aggregation and in turn
decreases transport efficiency. Of these stability factors,
luminal pH is of great interest as an increase in pH from
5.5 to 6.4 and 7.4 leads to a 3- and 10-fold drop in
nanoparticle transport, respectively. Since soluble chitosan
can act as an enhancer to increase paracellular transport by
up to 60%. this decrease is partially attributed to the
soluble chitosan precipitating near neutral pH. The
implication that chitosan-DNA nanoparticles are more stable
in the upper regions of the small intestine suggests that
higher uptake rates may occur in the duodenum compared to
the ileum and the colon. (C) 2009 Elsevier B.V. All rights
reserved.},
Key = {Article}
}
@article{Article,
Author = {Wang, Y. and Quek, C. H. and Leong, K.W. and Fang,
J.},
Title = {Synthesis and Cytotoxity of Luminescent InP Quantum
Dots},
Journal = {MRS Symposium Proceeding},
Volume = {1241E},
Year = {2010},
Key = {Article}
}
@article{Article,
Author = {Jiang, X. and Zheng, Y. and Chen, H. H. and Leong, K. W. and Wang, T. H. and Mao, H. Q.},
Title = {Dual-Sensitive Micellar Nanoparticles Regulate DNA Unpacking
and Enhance Gene-Delivery Efficiency},
Journal = {Adv Mater},
Year = {2010},
Key = {Article}
}
@article{Article,
Author = {Ho, Y. P. and Leong, K. W.},
Title = {Quantum dot-based theranostics},
Journal = {Nanoscale},
Volume = {2},
Number = {1},
Pages = {60-68},
Year = {2010},
Keywords = {resonance energy-transfer in-vivo semiconductor nanocrystals
gene delivery multifunctional nanoparticles intracellular
delivery gold nanoparticles cellular uptake sirna delivery
cancer-therapy},
Abstract = {Luminescent semiconductor nanocrystals, also known as
quantum dots (QDs), have advanced the fields of molecular
diagnostics and nanotherapeutics. Much of the initial
progress for QDs in biology and medicine has focused on
developing new biosensing formats to push the limit of
detection sensitivity. Nevertheless. QDs can be more than
passive bio-probes or labels for biological imaging and
cellular studies. The high surface-to-volume ratio of QDs
enables the construction of a "smart" multifunctional
nanoplatform, where the QDs serve not only as an imaging
agent but also a nanoscaffold catering for therapeutic and
diagnostic (theranostic) modalities. This mini review
highlights the emerging applications of functionalized QDs
as fluorescence contrast agents for imaging or as nanoscale
vehicles for delivery of therapeutics, with special
attention paid to the promise and challenges towards
QD-based theranostics.},
Key = {Article}
}
@article{Article,
Author = {Phua, K. and Leong, K. W.},
Title = {Microscale oral delivery devices incorporating
nanoparticles},
Journal = {Nanomedicine},
Volume = {5},
Number = {2},
Pages = {161-163},
Year = {2010},
Keywords = {system},
Key = {Article}
}
@article{Article,
Author = {Grigsby, C. L. and Leong, K. W.},
Title = {Balancing protection and release of DNA: tools to address a
bottleneck of non-viral gene delivery},
Journal = {Journal of the Royal Society Interface},
Volume = {7},
Pages = {S67-S82},
Year = {2010},
Keywords = {non-viral gene delivery nanomedicine biophotonics responsive
delivery nanoparticle polyplex resonance energy-transfer
bioreducible poly(amido amine)s multicellular tumor
spheroids plasmid DNA in-vitro correlation spectroscopy
extracellular-matrix intracellular trafficking transfection
efficiency polymer micelles},
Abstract = {Engineering polymeric gene-delivery vectors to release an
intact DNA payload at the optimal time and subcellular
compartment remains a formidable challenge. An ideal vector
would provide total protection of complexed DNA from
degradation prior to releasing it efficiently near or within
the nucleus of a target cell. While optimization of polymer
properties, such as molecular weight and charge density, has
proved largely inadequate in addressing this challenge,
applying polymeric carriers that respond to temperature,
light, pH and redox environment to trigger a switch from a
tight, protective complex to a more relaxed interaction
favouring release at the appropriate time and place has
shown promise. Currently, a paucity of gene carriers able to
satisfy the contrary requirements of adequate DNA protection
and efficient release contributes to the slow progression of
non-viral gene therapy towards clinical translation. This
review highlights the promising carrier designs that may
achieve an optimal balance of DNA protection and release. It
also discusses the imaging techniques and three-dimensional
in vitro models that can help study these two barriers in
the non-viral gene transfer process. Ultimately, efficacious
non-viral gene therapy will depend on the combination of
intelligent material design, innovative imaging techniques
and sophisticated in vitro model systems to facilitate the
rational design of polymeric gene-delivery
vectors.},
Key = {Article}
}
@article{Article,
Author = {Chalut, K. J. and Kulangara, K. and Giacomelli, M. G. and Wax, A. and Leong, K. W.},
Title = {Deformation of stem cell nuclei by nanotopographical
cues},
Journal = {Soft Matter},
Volume = {6},
Number = {8},
Pages = {1675-1681},
Year = {2010},
Keywords = {low-coherence interferometry smooth-muscle-cells
light-scattering membrane protein gene-expression
intact-cells soft media organization mechanotransduction
differentiation},
Abstract = {Cells sense cues in their surrounding microenvironment.
These cues are converted into intracellular signals and
transduced to the nucleus in order for the cell to respond
and adapt its function. Within the nucleus, structural
changes occur that ultimately lead to changes in the gene
expression. In this study, we explore the structural changes
of the nucleus of human mesenchymal stem cells as an effect
of topographical cues. We use a controlled nanotopography to
drive shape changes to the cell nucleus, and measure the
changes with both fluorescence microscopy and a novel light
scattering technique. The nucleus changes shape dramatically
in response to the nanotopography, and in a manner dependent
on the mechanical properties of the substrate. The kinetics
of the nuclear deformation follows an unexpected trajectory.
As opposed to a gradual shape change in response to the
topography, once the cytoskeleton attains an aligned and
elongation morphology on the time scale of several hours,
the nucleus changes shape rapidly and intensely.},
Key = {Article}
}
@article{Article,
Author = {Chen, S. and Jones, J. A. and Xu, Y. and Low, H. Y. and Anderson, J. M. and Leong, K. W.},
Title = {Characterization of topographical effects on macrophage
behavior in a foreign body response model},
Journal = {Biomaterials},
Volume = {31},
Number = {13},
Pages = {3479-91},
Year = {2010},
Abstract = {Current strategies to limit macrophage adhesion, fusion and
fibrous capsule formation in the foreign body response have
focused on modulating material surface properties. We
hypothesize that topography close to biological scale, in
the micron and nanometric range, provides a passive approach
without bioactive agents to modulate macrophage behavior. In
our study, topography-induced changes in macrophage behavior
was examined using parallel gratings (250 nm-2 mum line
width) imprinted on poly(epsilon-caprolactone) (PCL),
poly(lactic acid) (PLA) and poly(dimethyl siloxane) (PDMS).
RAW 264.7 cell adhesion and elongation occurred maximally on
500 nm gratings compared to planar controls over 48 h.
TNF-alpha and VEGF secretion levels by RAW 264.7 cells
showed greatest sensitivity to topographical effects, with
reduced levels observed on larger grating sizes at 48 h. In
vivo studies at 21 days showed reduced macrophage adhesion
density and degree of high cell fusion on 2 mum gratings
compared to planar controls. It was concluded that
topography affects macrophage behavior in the foreign body
response on all polymer surfaces examined.
Topography-induced changes, independent of surface
chemistry, did not reveal distinctive patterns but do affect
cell morphology and cytokine secretion in vitro, and cell
adhesion in vivo particularly on larger size topography
compared to planar controls.},
Key = {Article}
}
@article{Article,
Author = {Yim, E. K. F. and Darling, E. M. and Kulangara, K. and Guilak, F. and Leong, K. W.},
Title = {Nanotopography-induced changes in focal adhesions,
cytoskeletal organization, and mechanical properties of
human mesenchymal stem cells},
Journal = {Biomaterials},
Volume = {31},
Number = {6},
Pages = {1299-1306},
Year = {2010},
Keywords = {nanotopography mesenchymal stem cells focal adhesion cell
biomechanics cell-substrate interactions integrin
atomic-force microscopy viscoelastic properties
extracellular-matrix substrate proliferation stiffness
motility differentiation chondrocytes osteoblasts},
Abstract = {The growth of stem cells can be modulated by physical
factors such as extracellular matrix nanotopography. We
hypothesize that nanotopography modulates cell behavior by
changing the integrin clustering and focal adhesion (FA)
assembly, leading to changes in cytoskeletal organization
and cell mechanical properties. Human mesenchymal stem cells
(hMSCs) cultured on 350 nm gratings of tissue-culture
polystyrene (TCPS) and polydimethylsiloxane (PDMS) showed
decreased expression of integrin subunits alpha 2, alpha 6,
alpha V, beta 2, beta 3 and beta 4 compared to the
unpatterned controls. On gratings, the elongated hMSCs
exhibited an aligned actin cytoskeleton, while on
unpatterned controls, spreading cells showed a random but
denser actin cytoskeleton network. Expression of
cytoskeleton and FA components was also altered by the
nanotopography as reflected in the mechanical properties
measured by atomic force microscopy (AFM) indentation. On
the rigid TCPS, hMSCs on gratings exhibited lower
instantaneous and equilibrium Young's moduli and apparent
viscosity. On the softer PDMS, the effects of nanotopography
were not significant. However, hMSCs cultured on PDMS showed
lower cell mechanical properties than those on TCPS,
regardless of topography. These suggest that both
nanotopography and substrate stiffness could be important in
determining mechanical properties, while nanotopography may
be more dominant in determining the organization of the
cytoskeleton and FAs. (C) 2009 Elsevier Ltd. All rights
reserved.},
Key = {Article}
}
@article{Article,
Author = {Yow, S. Z. and Quek, C. H. and Yim, E. K. F. and Lim, C. T. and Leong, K. W.},
Title = {Collagen-based fibrous scaffold for spatial organization of
encapsulated and seeded human mesenchymal stem
cells},
Journal = {Biomaterials},
Volume = {30},
Number = {6},
Pages = {1133-1142},
Year = {2009},
Keywords = {mesenchymal stem cells cell encapsulation fibrous scaffold
collagen stem cell tissue engineering 3d cell patterning
polyelectrolyte complexation cellular infiltration
muscle-cells fiber differentiation bone proliferation
morphogenesis expression viability},
Abstract = {Living tissues consist of groups of cells organized in a
controlled manner to perform a specific function. Spatial
distribution of cells within a three-dimensional matrix is
critical for the success of any tissue-engineering
construct. Fibers endowed with cell-encapsulation capability
would facilitate the achievement of this objective. Here we
report the synthesis of a cell-encapsulated fibrous scaffold
by interfacial polyelectrolyte complexation (IPC) of
methylated collagen and a synthetic terpolymer. The collagen
component was well distributed in the fiber, which had a
mean ultimate tensile strength of 244.6 +/- 43.0 MPa.
Cultured in proliferating medium, human mesenchymal stem
cells (hMSCs) encapsulated in the fibers showed higher
proliferation rate than those seeded on the scaffold. Gene
expression analysis revealed the maintenance of multipotency
for both encapsulated and seeded samples up to 7 days as
evidenced by Sox 9, CBFA-1, AFP, PPAR gamma 2, nestin, GFAP,
collagen I, osteopontin and osteonectin genes. Beyond that,
seeded hMSCs started to express neuronal-specific genes such
as aggrecan and MAP2. The study demonstrates the appeal of
IPC for scaffold design in general and the promise of
collagen-based hybrid fibers for tissue engineering in
particular. It lays the foundation for building fibrous
scaffold that permits 3D spatial cellular organization and
mufti-cellular tissue development. 2008 (C) EIsevier Ltd.
All rights reserved.},
Key = {Article}
}
@article{Article,
Author = {Kunder, C. A. and John, A. L. S. and Li, G. J. and Leong, K.
W. and Berwin, B. and Staats, H. F. and Abraham, S.
N.},
Title = {Mast cell-derived particles deliver peripheral signals to
remote lymph nodes},
Journal = {Journal of Experimental Medicine},
Volume = {206},
Number = {11},
Pages = {2455-2467},
Year = {2009},
Keywords = {tumor-necrosis-factor high endothelial venules tnf-alpha
heparan-sulfate growth-factor t-cells degranulation release
granules mechanism},
Abstract = {During infection, signals from the periphery are known to
reach draining lymph nodes (DLNs), but how these molecules,
such as inflammatory cytokines, traverse the significant
distances involved without dilution or degradation remains
unclear. We show that peripheral mast cells, upon
activation, release stable submicrometer heparin-based
particles containing tumor necrosis factor and other
proteins. These complexes enter lymphatic vessels and
rapidly traffic to the DLNs. This physiological drug
delivery system facilitates communication between peripheral
sites of inflammation and remote secondary lymphoid
tissues.},
Key = {Article}
}
@article{Article,
Author = {Ho, Y.P. and Chen, H.H. and Leong, K.W. and Wang,
T.H.},
Title = {Combining QD-FRET and microfluidics to monitor DNA
nanocomplex self-assembly in real-time},
Journal = {J Vis Exp},
Pages = {1432},
Year = {2009},
Key = {Article}
}
@article{Article,
Author = {Kulangara, K. and Leong, K. W.},
Title = {Substrate topography shapes cell function},
Journal = {Soft Matter},
Volume = {5},
Number = {21},
Pages = {4072-4076},
Year = {2009},
Keywords = {hematopoietic stem/progenitor cells focal adhesion kinase
electrospun nanofibers natural lithography contact guidance
nanoscale tissue force polystyrene expansion},
Abstract = {Influencing cell behavior from proliferation to
differentiation using substrate or implant topography is an
attractive strategy for regenerative medicine applications.
Substrate topography at the submicron range is of particular
interest because the size range is comparable to
extracellular matrix structures. Emerging literature
presents many interesting findings on how nanotopography
enhances cell adhesion, alters cell morphology, affects
proliferation, initiates intracellular signaling, provides
contact guidance and mediates stem cell differentiation.
Incorporating topographical consideration into the design of
a biomimetic microenvironment for cell culture will become
increasingly important in light of these studies and
practical with advances in nanofabrication technologies.
This Highlight underscores the promise of and the unknown
information about topographical effects in manipulating
cell-substrate interaction and advancing tissue
engineering.},
Key = {Article}
}
@article{Article,
Author = {Chakraborty, S. and Liao, I. C. and Adler, A. and Leong, K.
W.},
Title = {Electrohydrodynamics: A facile technique to fabricate drug
delivery systems},
Journal = {Advanced Drug Delivery Reviews},
Volume = {61},
Number = {12},
Pages = {1043-1054},
Year = {2009},
Keywords = {electrospinning electrospraying nanofiber nanoparticle drug
delivery systems core-shell nanofibers coaxial
electrospinning controlled release tissue engineering
cone-jet mode in-vitro electrospun nanofibers polymer
nanofibers composite fibers controlled-release
sustained-release block-copolymers ultrafine fibers
particle-size},
Abstract = {Electrospinning and electrospraying are facile
electrohydrodynamic fabrication methods that can generate
drug delivery systems (DDS) through a one-step process. The
nanostructured fiber and particle morphologies produced by
these techniques offer tunable release kinetics applicable
to diverse biomedical applications. Coaxial
electrospinning/electrospraying, a relatively new technique
of fabricating core-shell fibers/particles have added to the
versatility of these DDS by affording a near zero-order drug
release kinetics, dampening of burst release, and
applicability to a wider range of bioactive agents.
Controllable electrospinning/spraying of fibers and
particles and subsequent drug release from these chiefly
polymeric vehicles depends on well-defined solution and
process parameters. The additional drug delivery capability
from electrospun fibers can further enhance the material's
functionality in tissue engineering applications. This
review discusses the state-of-the-art of using
electrohydrodynamic technique to generate
nanofiber/particles as drug delivery devices. (c) 2009
Elsevier B.V. All rights reserved.},
Key = {Article}
}
@article{Article,
Author = {Oney, S. and Lam, R. T. S. and Bompiani, K. M. and Blake, C.
M. and Quick, G. and Heidel, J. D. and Liu, J. Y. C. and Mack, B. C. and Davis, M. E. and Leong, K. W. and Sullenger,
B. A.},
Title = {Development of universal antidotes to control aptamer
activity},
Journal = {Nature Medicine},
Volume = {15},
Number = {10},
Pages = {1224-1228},
Year = {2009},
Keywords = {von-willebrand-factor adverse drug events cardiopulmonary
bypass protamine sulfate rna aptamers factor-ixa t-cells
sirna therapeutics angiogenesis},
Abstract = {With an ever increasing number of people taking numerous
medications, the need to safely administer drugs and limit
unintended side effects has never been greater. Antidote
control remains the most direct means to counteract acute
side effects of drugs, but, unfortunately, it has been
challenging and cost prohibitive to generate antidotes for
most therapeutic agents. Here we describe the development of
a set of antidote molecules that are capable of
counteracting the effects of an entire class of therapeutic
agents based upon aptamers. These universal antidotes
exploit the fact that, when systemically administered,
aptamers are the only free extracellular oligonucleotides
found in circulation. We show that protein- and
polymer-based molecules that capture oligonucleotides can
reverse the activity of several aptamers in vitro and
counteract aptamer activity in vivo. The availability of
universal antidotes to control the activity of any aptamer
suggests that aptamers may be a particularly safe class of
therapeutics.},
Key = {Article}
}
@article{Article,
Author = {Chen, H. H. and Ho, Y. P. and Jiang, X. and Mao, H. Q. and Wang, T. H. and Leong, K. W.},
Title = {Simultaneous non-invasive analysis of DNA condensation and
stability by two-step QD-FRET},
Journal = {Nano Today},
Volume = {4},
Number = {2},
Pages = {125-134},
Year = {2009},
Keywords = {nanocomplex fret quantum dot delivery degradation nonviral
resonance energy-transfer quantum-dot-fret gene delivery
intrabiliary infusion potential barrier living cells
nanoparticles unpacking tool transfection},
Abstract = {Nanoscale vectors comprised of cationic polymers that
condense DNA to form nanocomplexes are promising options for
gene transfer. The rational design of more efficient
nonviral gene carriers will be possible only with better
mechanistic understanding of the critical rate-limiting
steps, such as nanocomplex unpacking to release DNA and
degradation by nucleases. We present a two-step quantum dot
fluorescence resonance energy transfer (two-step QD-FRET)
approach to simultaneously and non-invasively analyze DNA
condensation and stability. Plasmid DNA, double-labeled with
QD (525 nm emission) and nucleic acid dyes, were complexed
with Cy5-labeled cationic gene carriers. The QD donor drives
energy transfer step-wise through the intermediate nucleic
acid dye to the final acceptor Cy5. At least three distinct
states of DNA condensation and integrity were distinguished
in single particle manner and within cells by quantitative
ratiometric analysis of energy transfer efficiencies. This
novel two-step QD-FRET method allows for more detailed
assessment of the onset of DNA release and degradation
simultaneously. (C) 2009 Elsevier Ltd. All rights
reserved.},
Key = {Article}
}
@article{Article,
Author = {Ho, Y. P. and Chen, H. H. and Leong, K. W. and Wang, T.
H.},
Title = {The convergence of quantum-dot-mediated fluorescence
resonance energy transfer and microfluidics for monitoring
DNA polyplex self-assembly in real time},
Journal = {Nanotechnology},
Volume = {20},
Number = {9},
Pages = {-},
Year = {2009},
Keywords = {gene-therapy progress delivery chitosan nanoparticles
complexes efficiency condensation channels flow
deacetylation},
Abstract = {We present a novel convergence of quantum-dot-mediated
fluorescence resonance energy transfer (QD-FRET) and
microfluidics, through which molecular interactions were
precisely controlled and monitored using highly sensitive
quantum-dot-mediated FRET. We demonstrate its potential in
studying the kinetics of self-assembly of DNA polyplexes
under laminar flow in real time with millisecond resolution.
The integration of nanophotonics and microfluidics offers a
powerful tool for elucidating the formation of
polyelectrolyte polyplexes, which is expected to provide
better control and synthesis of uniform and customizable
polyplexes for future nucleic acid-based
therapeutics.},
Key = {Article}
}
@article{Article,
Author = {Liao, I. C. and Chen, S. L. and Liu, J. B. and Leong, K.
W.},
Title = {Sustained viral gene delivery through core-shell
fibers},
Journal = {Journal of Controlled Release},
Volume = {139},
Number = {1},
Pages = {48-55},
Year = {2009},
Keywords = {viral gene therapy substrate-mediated delivery tissue
engineering electrospinning localized gene delivery
recombinant adenovirus in-vivo vectors therapy nanofibers
release optimization expression scaffolds
antibody},
Abstract = {Although viral gene transfer is efficient in achieving
transgene expression for tissue engineering, drawbacks of
virus dissemination, toxicity and transient gene expression
due to immune response have hindered its widespread
application. Many tissue engineering studies thus opt to
genetically engineer cells in vitro prior to their
introduction in vivo. However, it would be attractive to
obviate the need for in vitro manipulation by transducing
the infiltrating progenitor cells in situ. This study
introduces the fabrication of a virus-encapsulated
electrospun fibrous scaffold to achieve sustained and
localized transduction. Adenovirus encoding the gene for
green fluorescent protein was efficiently encapsulated into
the core of poly(epsilon-caprolactone) fibers through
co-axial electrospinning and was subsequently released via a
porogen-mediated process. HEK 293 cells seeded on the
scaffolds expressed high level of transgene expression over
a month, while cells inoculated by scaffold supernatant
showed only transient expression for a week. RAW 264.7 cells
cultured on the virus-encapsulated fibers produced a lower
level of IL-1 beta, TNF-alpha and IFN-alpha, suggesting that
the activation of macrophage cells by the viral vector was
reduced when encapsulated in the core-shell PCL fibers. in
demonstrating sustained and localized cell tramsduction,
this study presents an attractive alternative mode of
applying viral gene transfer for regenerative medicine. (C)
2009 Elsevier B.V. All rights reserved.},
Key = {Article}
}
@article{Article,
Author = {Lou, Y. L. and Peng, Y. S. and Chen, B. H. and Wang, L. F. and Leong, K. W.},
Title = {Poly(ethylene imine)-g-chitosan using EX-810 as a spacer for
nonviral gene delivery vectors},
Journal = {Journal of Biomedical Materials Research Part
A},
Volume = {88A},
Number = {4},
Pages = {1058-1068},
Year = {2009},
Keywords = {chitosan poly(ethylene imine) polyplex transfection
cytotoxicity low-molecular-weight chitosan-graft-polyethylenimine
in-vitro DNA delivery transfection efficiency plasmid DNA
nanoparticles carrier copolymers complexes},
Abstract = {Polyelectrolyte complexes have been widely studied as gene
carriers in recent years. In this study, poly (ethylene
imine) was grafted onto chitosan (PEI-g-CHI) as a nonviral
gene carrier in order to improve the water solubility as
well as the inherent transfection efficiency of chitosan. We
present a novel method to conjugate the amine or hydroxyl
groups of chitosan (CHI) and the amine groups of PEI through
opening the epoxide rings of ethylene glycol diglycidyl
ether (EX-810), which also brings the merits as mentioned in
PEGylation chemistry. The degree of substitution of PEI onto
CHI was characterized by NMR. The preliminarily cellular
mechanisms, from the cellular entry to the endosomal
release, were investigated by the correlations among the
physicochemical properties of the DNA-polymer complexes, the
buffering capacity of the modified polymer, the
cytotoxicity, and the efficiency of the transgene
expression. The cytotoxicity assayed by MTT shows that cell
viability of PEI-g-CHI is higher than CHI especially
noticeable at high concentrations using human kidney 293T
cells. The efficiency of transgene expression and the amount
of intracellular plasmid were monitored using green
fluorescent protein (GFP) and visualized by fluorescence
microscopy. The transfection efficiency of PEI-g-CHI/DNA
polyplex is significantly better than CHI/DNA polyplex when
using the weight ratios higher than 2.5. (c) 2008 Wiley
Periodicals, Inc. J Biomed Mater Res 88A: 1058-1068,
2009},
Key = {Article}
}
@article{Article,
Author = {Chew, S. Y. and Mi, R. and Hoke, A. and Leong, K.
W.},
Title = {The effect of the alignment of electrospun fibrous scaffolds
on Schwann cell maturation},
Journal = {Biomaterials},
Volume = {29},
Number = {6},
Pages = {653-61},
Year = {2008},
Keywords = {Base Sequence DNA Primers Humans Polymerase Chain Reaction
Schwann Cells/*cytology Tissue Engineering},
Abstract = {Peripheral nerve regeneration can be enhanced by the
stimulation of formation of bands of Bungner prior to
implantation. Aligned electrospun poly(epsilon-caprolactone)
(PCL) fibers were fabricated to test their potential to
provide contact guidance to human Schwann cells. After 7
days of culture, cell cytoskeleton and nuclei were observed
to align and elongate along the fiber axes, emulating the
structure of bands of Bungner. Microarray analysis revealed
a general down-regulation in expression of neurotrophin and
neurotrophic receptors in aligned cells as compared to cells
seeded on two-dimensional PCL film. Real-time-PCR analyses
confirmed the up-regulation of early myelination marker,
myelin-associated glycoprotein (MAG), and the
down-regulation of NCAM-1, a marker of immature Schwann
cells. Similar gene expression changes were also observed on
cells cultured on randomly oriented PCL electrospun fibers.
However, up-regulation of the myelin-specific gene, P0, was
observed only on aligned electrospun fibers, suggesting the
propensity of aligned fibers in promoting Schwann cell
maturation.},
Key = {Article}
}
@article{Article,
Author = {Chen, H. H. and Ho, Y. P. and Jiang, X. and Mao, H. Q. and Wang, T. H. and Leong, K. W.},
Title = {Quantitative comparison of intracellular unpacking kinetics
of polyplexes by a model constructed from quantum
Dot-FRET},
Journal = {Molecular Therapy},
Volume = {16},
Number = {2},
Pages = {324-332},
Year = {2008},
Keywords = {chitosan-DNA nanoparticles resonance energy-transfer gene
delivery polyethylenimine/DNA complexes plasmid DNA
efficiency polymers transfection expression
vector},
Abstract = {A major challenge for non-viral gene delivery is gaining a
mechanistic understanding of the rate-limiting steps. A
critical barrier in polyplex-mediated gene delivery is the
timely unpacking of polyplexes within the target cell to
liberate DNA for efficient gene transfer. In this study, the
component plasmid DNA and polymeric gene carrier were
individually labeled with quantum dots (QDs) and Cy5 dyes,
respectively, as a donor and acceptor pair for fluorescence
resonance energy transfer (FRET). The high signal-to-noise
ratio in QD-mediated FRET enabled sensitive detection of
discrete changes in polyplex stability. The intracellular
uptake and dissociation of polyplexes through QD-FRET was
captured over time by confocal microscopy. From quantitative
image - based analysis, distributions of released plasmid
within the endo/ lysosomal, cytosolic, and nuclear
compartments formed the basis for constructing a
three-compartment first-order kinetics model. Polyplex
unpacking kinetics for chitosan, polyethylenimine, and
polyphosphoramidate were compared and found to correlate
well with transfection efficiencies. Thus, QD-FRET-enabled
detection of polyplex stability combined with image-based
quantification is a valuable method for studying mechanisms
involved in polyplex unpacking and trafficking within live
cells. We anticipate that this method will also aid the
design of more efficient gene carriers.},
Key = {Article}
}
@article{Article,
Author = {Chan, B. P. and Leong, K. W.},
Title = {Scaffolding in tissue engineering: general approaches and
tissue-specific considerations},
Journal = {European Spine Journal},
Volume = {17},
Pages = {S467-S479},
Year = {2008},
Keywords = {tissue engineering scaffolding scaffolds biomaterials
intervertebral disc mesenchymal stem-cells small-intestinal
submucosa intervertebral disc degeneration nucleus pulposus
replacement photochemical cross-linking bipedal animal-model
extracellular-matrix annulus fibrosus in-vitro
photopolymerizable hydrogels},
Abstract = {Scaffolds represent important components for tissue
engineering. However, researchers often encounter an
enormous variety of choices when selecting scaffolds for
tissue engineering. This paper aims to review the functions
of scaffolds and the major scaffolding approaches as
important guidelines for selecting scaffolds and discuss the
tissue-specific considerations for scaffolding, using
intervertebral disc as an example.},
Key = {Article}
}
@article{Article,
Author = {Tsurushima, H. and Yuan, X. and Dillehay, L. E. and Leong,
K. W.},
Title = {Radiation-inducible caspase-8 gene therapy for malignant
brain tumors},
Journal = {International Journal of Radiation Oncology Biology
Physics},
Volume = {71},
Number = {2},
Pages = {517-525},
Year = {2008},
Keywords = {radiation-inducible gene therapy caspase-8 gene therapy
combined gene and radiation therapy malignant glioma in vivo
electroporation human prostate-cancer ionizing-radiation
in-vivo hepatocellular-carcinoma glioma-cells p53 gene
apoptosis growth activation expression},
Abstract = {Purpose: Patients with malignant gliomas have a poor
prognosis. To explore a novel and more effective approach
for the treatment of patients with malignant gliomas, we
designed a strategy that combines caspase-8 (CSP8) gene
therapy and radiation treatment (RT). In addition, the
specificity of the combined therapy was investigated to
decrease the unpleasant effects experienced by the
surrounding normal tissue. Methods and Materials: We
constructed the plasmid pEGR-green fluorescence protein that
included the radiation-inducible early growth response
gene-1 (Egr-1) promoter and evaluated its characteristics.
The pEGR-CSP8 was constructed and included the Egr-1
promoter and CSP8 complementary DNA. Assays that evaluated
the apoptosis inducibility and cytotoxicity caused by CSP8
gene therapy combined with RT were performed using U251 and
U87 glioma cells. The pEGR-CSP8 was transfected into the
subcutaneous U251 glioma cells of nude mice by means of in
vivo electroporation. The in vivo effects of CSP8 gene
therapy combined with RT were evaluated. Results: The Egr-1
promoter yielded a better response with fractionated RT than
with single-dose RT. In the assay of apoptosis inducibility
and cytotoxicity, pEGR-CSP8 showed response for RT. The
pEGR-CSP8 combined with RT is capable of inducing cell death
effectively. In mice treated with pEGR-CSP8 and RT,
apoptotic cells were detected in pathologic sections, and a
significant difference was observed in tumor volumes.
Conclusions: Our results indicate that radiation-inducible
gene therapy may have great potential because this can be
spatially or temporally controlled by exogenous RT and is
safe and specific. (C) 2008 Elsevier Inc.},
Key = {Article}
}
@article{Article,
Author = {Bowman, K. and Sarkar, R. and Raut, S. and Leong, K.
W.},
Title = {Gene transfer to hemophilia A mice via oral delivery of
FVIII-chitosan nanoparticles},
Journal = {Journal of Controlled Release},
Volume = {132},
Number = {3},
Pages = {252-259},
Year = {2008},
Keywords = {non-viral gene delivery hemophilia therapy chitosan oral
delivery gene medicine human-factor-viii DNA nanoparticles
particle-size therapy expression vectors nanospheres
derivatives efficiency mutations},
Abstract = {Effective oral delivery of a non-viral gene carrier would
represent a novel and attractive strategy for therapeutic
gene transfer. To evaluate the potential of this approach,
we studied the oral gene delivery efficacy of DNA polyplexes
composed of chitosan and Factor VIII DNA. Transgene DNA was
detected in both local and systemic tissues following oral
administration of the chitosan nanoparticles to hemophilia A
mice. Functional factor VIII protein was detected in plasma
by chromogenic and thrombin generation assays, reaching a
peak level of 2-4% FVIII at day 22 after delivery. In
addition, a bleeding challenge one month after DNA
administration resulted in phenotypic correction in 13/20
mice given 250-600 mu g of FVIII DNA in chitosan
nanoparticles, compared to 1/13 mice given naked FVIII DNA
and 0/6 untreated mice. While further optimization would be
required to render this type of delivery system practical
for hemophilia A gene therapy, the findings suggest the
feasibility of oral, non-viral delivery for gene medicine
applications. (C) 2008 Elsevier B.V. All rights
reserved.},
Key = {Article}
}
@article{Article,
Author = {Choi, J. S. and Leong, K. W. and Yoo, H.
S.},
Title = {In vivo wound healing of diabetic ulcers using electrospun
nanofibers immobilized with human epidermal growth factor
(EGF)},
Journal = {Biomaterials},
Volume = {29},
Number = {5},
Pages = {587-96},
Year = {2008},
Keywords = {Animals Cells, Cultured Diabetic Angiopathies/drug
therapy/*pathology *Electrons Epidermal Growth
Factor/*pharmacology/therapeutic use Female Humans
Immunohistochemistry Mice Mice, Inbred C57BL Molecular
Structure Nanostructures/*chemistry Recombinant
Proteins/therapeutic use Wound Healing/*drug
effects},
Abstract = {Biodegradable polymers were electrospun and recombinant
human epidermal growth factor (EGF) was immobilized on the
electrospun nanofibers for the purpose of treating diabetic
ulcers. Amine-terminated block copolymers composed of
poly(epsilon-caprolactone) [PCL] and poly(ethyleneglycol)
[PEG] and PCL were electrospun to biocompatible nanofibers
with functional amine groups on the surface via PEG linkers.
EGF was chemically conjugated to the surface of the
nanofibers. The conjugation amount of EGF on the nanofibers
was quantitated by X-ray photoelectron scattering. Human
primary keratinocytes were cultivated on EGF-conjugated
nanofibers in order to investigate the effect of EGF
nanofibers on the differentiation of keratinocytes. Wound
healing effects of the EGF nanofibers were confirmed in
diabetic animals with dorsal wounds. The expression of
keratinocyte-specific genes significantly increased with
application of EGF-conjugated nanofibers. The EGF-nanofibers
exerted superior in vivo wound healing activities compared
to control groups or EGF solutions. Furthermore,
immunohistochemical-staining results showed that
EGF-receptor (EGFR) was highly expressed in the EGF
nanofiber group. This study showed that EGF-conjugated
nanofiber could potentially be employed as a novel wound
healing material by increasing proliferation and phenotypic
expression of keratinocytes.},
Key = {Article}
}
@article{Article,
Author = {Liao, I. C. and Liu, J. B. and Bursac, N. and Leong, K.
W.},
Title = {Effect of Electromechanical Stimulation on the Maturation of
Myotubes on Aligned Electrospun Fibers},
Journal = {Cellular and Molecular Bioengineering},
Volume = {1},
Number = {2-3},
Pages = {133-145},
Year = {2008},
Keywords = {nanotopography tissue engineering skeletal muscle
electromechanical stimulation biomimetic microenvironment
regenerative medicine nanofibers skeletal-muscle myoblasts
in-vitro c2c12 myotubes differentiation cells activation
proteins transplantation transcription morphology},
Abstract = {Tissue engineering may provide an alternative to cell
injection as a therapeutic solution for myocardial
infarction. A tissue-engineered muscle patch may offer
better host integration and higher functional performance.
This study examined the differentiation of skeletal
myoblasts on aligned electrospun polyurethane (PU) fibers
and in the presence of electromechanical stimulation.
Skeletal myoblasts cultured on aligned PU fibers showed more
pronounced elongation, better alignment, higher level of
transient receptor potential cation channel-1 (TRPC-1)
expression, upregulation of contractile proteins and higher
percentage of striated myotubes compared to those cultured
on random PU fibers and film. The resulting tissue
constructs generated tetanus forces of 1.1 mN with a 10-ms
time to tetanus. Additional mechanical, electrical, or
synchronized electromechanical stimuli applied to myoblasts
cultured on PU fibers increased the percentage of striated
myotubes from 70 to 85% under optimal stimulation
conditions, which was accompanied by an upregulation of
contractile proteins such as alpha-actinin and myosin heavy
chain. In describing how electromechanical cues can be
combined with topographical cue, this study helped move
towards the goal of generating a biomimetic microenvironment
for engineering of functional skeletal muscle.},
Key = {Article}
}
@article{Article,
Author = {Prow, T. W. and Bhutto, I. and Kim, S. Y. and Grebe, R. and Merges, C. and McLeod, D. S. and Uno, K. and Mennon, M. and Rodriguez, L. and Leong, K. and Lutty, G.
A.},
Title = {Ocular nanoparticle toxicity and transfection of the retina
and retinal pigment epithelium},
Journal = {Nanomedicine-Nanotechnology Biology and Medicine},
Volume = {4},
Number = {4},
Pages = {340-349},
Year = {2008},
Keywords = {chitosan magnetic nanoparticle gene delivery retina toxicity
gene delivery chitosan nanoparticles in-vivo localization
efficiency diseases system cells liver},
Abstract = {Chitosan, PCEP (poly{[(cholesteryl oxocarbonylamido ethyl)
methyl bis(ethylene) ammonium iodide] ethyl phosphate}), and
magnetic nanoparticles (MNPs) were evaluated for the safe
delivery of genes in the eye. Rabbits were injected with
nanoparticles either intravitreally (IV) or subretinally
(SR) and sacrificed 7 days later. Eyes were grossly
evaluated for retinal pigment epithelium abnormalities,
retinal degeneration, and inflammation. All eyes were
cryopreserved and sectioned for analysis of toxicity and
expression of either enhanced green or red fluorescent
proteins. All of the nanoparticles were able to transfect
cells in vitro and in vivo. IV chitosan showed inflammation
in 12/13 eyes, whereas IV PCEP and IV MNPs were not
inflammatory and did not induce retinal pathology. SR PCEP
was nontoxic in the majority of cases but yielded poor
transfection, whereas SR MNPs were nontoxic and yielded good
transfection. Therefore, we conclude that the best
nanoparticle evaluated in vivo was the least toxic
nanoparticle tested, the MNP. (c) 2008 Elsevier Inc. All
rights reserved.},
Key = {Article}
}
@article{Article,
Author = {Tan, S. C. W. and Pan, W. X. and Ma, G. and Cai, N. and Leong, K. W. and Liao, K.},
Title = {Viscoelastic behaviour of human mesenchymal stem
cells},
Journal = {Bmc Cell Biology},
Volume = {9},
Pages = {-},
Year = {2008},
Keywords = {midpalatal suture cartilage compressive force chondrogenic
differentiation living cells promotes mechanotransduction
microtubules cytoskeleton expression collagen},
Abstract = {Background: In this study, we have investigated the
viscoelastic behaviour of individual human adult bone
marrow-derived mesenchymal stem cells (hMSCs) and the role
of F-actin filaments in maintaining these properties, using
micropipette aspiration technique together with a standard
linear viscoelastic solid model.},
Key = {Article}
}
@article{Article,
Author = {Chalut, K. J. and Chen, S. and Finan, J. D. and Giacomelli,
M. G. and Guilak, F. and Leong, K. W. and Wax,
A.},
Title = {Label-free, high-throughput measurements of dynamic changes
in cell nuclei using angle-resolved low coherence
interferometry},
Journal = {Biophysical Journal},
Volume = {94},
Number = {12},
Pages = {4948-4956},
Year = {2008},
Keywords = {articular chondrocytes light-scattering spectroscopy
morphology scale},
Abstract = {Accurate measurements of nuclear deformation, i.e.,
structural changes of the nucleus in response to
environmental stimuli, are important for signal transduction
studies. Traditionally, these measurements require labeling
and imaging, and then nuclear measurement using image
analysis. This approach is time-consuming, invasive, and
unavoidably perturbs cellular systems. Light scattering, an
emerging biophotonics technique for probing physical
characteristics of living systems, offers a promising
alternative. Angle-resolved low-coherence interferometry
(a/LCI), a novel light scattering technique, was developed
to quantify nuclear morphology for early cancer detection.
In this study, a/LCI is used for the first time to
noninvasively measure small changes in nuclear morphology in
response to environmental stimuli. With this new
application, we broaden the potential uses of a/LCI by
demonstrating high-throughput measurements and by probing
aspherical nuclei. To demonstrate the versatility of this
approach, two distinct models relevant to current
investigations in cell and tissue engineering research are
used. Structural changes in cell nuclei due to subtle
environmental stimuli, including substrate topography and
osmotic pressure, are profiled rapidly without disrupting
the cells or introducing artifacts associated with
traditional measurements. Accuracy >= 3% is obtained for the
range of nuclear geometries examined here, with the greatest
deviations occurring for the more complex geometries. Given
the high-throughput nature of the measurements, this
deviation may be acceptable for many biological applications
that seek to establish connections between morphology and
function.},
Key = {Article}
}
@article{Article,
Author = {Haider, M. and Cappello, J. and Ghandehari, H. and Leong, K.
W.},
Title = {In vitro chondrogenesis of mesenchymal stem cells in
recombinant silk-elastinlike hydrogels},
Journal = {Pharmaceutical Research},
Volume = {25},
Number = {3},
Pages = {692-699},
Year = {2008},
Keywords = {chondrogenesis genetically engineered polymers hydrogels
silk-elastinelike polymers tissue engineering protein
polymer bone-marrow articular-cartilage controlled-release
drug-delivery tissue-repair gene-therapy matrix
differentiation polypeptide},
Abstract = {Purpose. In this study the chondrocytic differentiation and
cartilage matrix accumulation of human mesenchymal stem
cells (hMSCs) were investigated after encapsulation in a
genetically engineered silk-elastinlike protein polymer
SELP-47 K as an injectable matrix for delivery of cell-based
therapeutics. Materials and Methods. hMSCs were encapsulated
in SELP-47 K and cultured for 4 weeks in chondrogenic medium
with or without transforming growth factor-beta 3 (TGF).
Chondrogenic differentiation was evaluated by histological,
RNA and biochemical analyses for the expression of cartilage
extracellular matrix components. Results. Histological and
immunohistochemical staining revealed that the cells
acquired a rounded morphology and were embedded in
significant amounts of chondrogenic extracellular matrix.
Reverse transcriptase (RT)-PCR showed an up-regulation in
aggrecan, type II and type X collagen and SOX9 in presence
of TGF-beta 3. By day 28, constructs cultured in the
presence of TGF-beta 3 exhibited significant increase in
sulfated glycosaminoglycan and total collagen content up to
65 and 300%, respectively. Conclusions. This study
demonstrates that SELP-47 K hydrogel can be used as a
scaffold for encapsulation and chondrogenesis of hMSCs. The
ability to use recombinant techniques to precisely control
SELP structure enables the investigation of injectable
protein polymer scaffolds for soft-tissue engineering with
varied physicochemical properties.},
Key = {Article}
}
@booklet{Bursac07,
Author = {N. Bursac and Y. H. Loo and K. Leong and L.
Tung},
Title = {Novel anisotropic engineered cardiac tissues: Studies of
electrical propagation},
Journal = {Biochemical And Biophysical Research Communications},
Volume = {361},
Number = {4},
Pages = {847 -- 853},
Year = {2007},
Month = {October},
ISSN = {0006-291X},
Abstract = {The goal of this study was to engineer cardiac tissue
constructs with uniformly anisotropic architecture, and to
evaluate their electrical function using multi-site optical
mapping of cell membrane potentials. Anisotropic polymer
scaffolds made by leaching of aligned sucrose templates were
seeded with neonatal rat cardiac cells and cultured in
rotating bioreactors for 6-14 days. Cells aligned and
interconnected inside the scaffolds and when stimulated by a
point electrode, supported macroscopically continuous,
anisotropic impulse propagation. By culture day 14, the
ratio of conduction velocities along vs. across cardiac
fibers reached a value of 2, similar to that in native
neonatal ventricles, while action potential duration and
maximum capture rate, respectively, decreased to 120 ms and
increased to similar to 5 Hz. The shorter culture time and
larger scaffold thickness were associated with increased
incidence of sustained reentrant arrhythmias. In summary,
this study is the first successful attempt to engineer a
cm(2)-size, functional anisotropic cardiac tissue patch. (C)
2007 Elsevier Inc. All rights reserved.},
Key = {Bursac07}
}
@article{070110350899,
Author = {Chen, Beiyi and Dang, Jiyoung and Tan, Tuan Lin and Fang,
Ning and Chen, Wei Ning and Leong, Kam W. and Chan,
Vincent},
Title = {Dynamics of smooth muscle cell deadhesion from
thermosensitive hydroxybutyl chitosan},
Journal = {Biomaterials},
Volume = {28},
Number = {8},
Pages = {1503 - 1514},
Year = {2007},
url = {http://dx.doi.org/10.1016/j.biomaterials.2006.11.027},
Keywords = {Muscle;Organic polymers;Hydrophilicity;Adhesion;Tissue
culture;RNA;Atomic force microscopy;},
Abstract = {Thermoresponsive polymer (TRP) enables the enzyme-free
harvesting of cells through an acute increase in surface
hydrophilicity of TRP across its lower critical solution
temperature (LCST), rendering feasible the generation of
polymer-free cell sheets for regenerative medicine
applications. To date, the intricate mechanisms of cell
deadhesion/detachment on TRP surface remain obscure.
Elucidation of such biophysical responses would be valuable
for the cell sheet technology. In this study, integrative
biophysical techniques are applied to probe the
thermal-induced deadhesion kinetics of smooth muscle cell
(SMC) on thermoresponsive hydroxybutyl chitosan (HBC29)
against different periods of pre-culture time at 37 °C.
Atomic force microscopy demonstrates that both the surface
topography and mechanical property of HBC29 film in water
are acutely modulated across its LCST. Firstly, cells show
negligible changes in adhesion contact area during
low-temperature incubation on unmodified tissue culture
polystyrene (TCPS). Secondly, the recession of adhesion
contact and retraction of cell body for cells with different
pre-culture times are triggered by HBC29 coating on TCPS.
Interestingly, the initial rate of reduction in the
normalized adhesion contact area of SMC is negatively
correlated with the pre-culture time. Thirdly, the degree of
cell deformation and average adhesion energy are reducing
functions of time only for SMCs with the lowest pre-culture
time. In contrast, adhesion energy per cell is a reducing
function of time irrespective of the change of pre-culture
time. Lastly, the temporal dynamics of cytoskeleton
organization and β-actin/smoothelin-B mRNA expression
for SMCs is strongly dependent on the pre-culture time.
Overall, this study demonstrates that the thermal-induced
deadhesion of SMC on TRP is characterized by the evolution
of its contractile phenotypes. © 2006 Elsevier Ltd. All
rights reserved.},
Key = {070110350899}
}
@article{Article,
Author = {Chen, B. and Dang, J. and Tan, T. L. and Fang, N. and Chen,
W. N. and Leong, K. W. and Chan, V.},
Title = {Dynamics of smooth muscle cell deadhesion from
thermosensitive hydroxybutyl chitosan},
Journal = {Biomaterials},
Volume = {28},
Number = {8},
Pages = {1503-14},
Year = {2007},
Abstract = {Thermoresponsive polymer (TRP) enables the enzyme-free
harvesting of cells through an acute increase in surface
hydrophilicity of TRP across its lower critical solution
temperature (LCST), rendering feasible the generation of
polymer-free cell sheets for regenerative medicine
applications. To date, the intricate mechanisms of cell
deadhesion/detachment on TRP surface remain obscure.
Elucidation of such biophysical responses would be valuable
for the cell sheet technology. In this study, integrative
biophysical techniques are applied to probe the
thermal-induced deadhesion kinetics of smooth muscle cell
(SMC) on thermoresponsive hydroxybutyl chitosan (HBC29)
against different periods of pre-culture time at 37 degrees
C. Atomic force microscopy demonstrates that both the
surface topography and mechanical property of HBC29 film in
water are acutely modulated across its LCST. Firstly, cells
show negligible changes in adhesion contact area during
low-temperature incubation on unmodified tissue culture
polystyrene (TCPS). Secondly, the recession of adhesion
contact and retraction of cell body for cells with different
pre-culture times are triggered by HBC29 coating on TCPS.
Interestingly, the initial rate of reduction in the
normalized adhesion contact area of SMC is negatively
correlated with the pre-culture time. Thirdly, the degree of
cell deformation and average adhesion energy are reducing
functions of time only for SMCs with the lowest pre-culture
time. In contrast, adhesion energy per cell is a reducing
function of time irrespective of the change of pre-culture
time. Lastly, the temporal dynamics of cytoskeleton
organization and beta-actin/smoothelin-B mRNA expression for
SMCs is strongly dependent on the pre-culture time. Overall,
this study demonstrates that the thermal-induced deadhesion
of SMC on TRP is characterized by the evolution of its
contractile phenotypes.},
Key = {Article}
}
@article{Article,
Author = {Park, D. J. and Choi, J. H. and Leong, K. W. and Kwon, J. W. and Eun, H. S.},
Title = {Tissue-engineered bone formation with gene transfer and
mesenchymal stem cells in a minimally invasive
technique},
Journal = {Laryngoscope},
Volume = {117},
Number = {7},
Pages = {1267-71},
Year = {2007},
Keywords = {Alginates/administration & dosage/pharmacology Animals
Biocompatible Materials/administration & dosage/pharmacology
Bone Morphogenetic Proteins/*genetics Bone and
Bones/cytology/drug effects Cell Line Chitosan/administration
& dosage/pharmacology DNA/genetics Drug Combinations Gels
*Gene Transfer Techniques Glucuronic Acid/administration &
dosage/pharmacology Hexuronic Acids/administration &
dosage/pharmacology Mesenchymal Stem Cell
Transplantation/*methods Mice Mice, Nude
Osteogenesis/*genetics Plasmids/genetics Receptor
Protein-Tyrosine Kinases/genetics Surgical Procedures,
Minimally Invasive/methods Tissue Engineering/*methods
Transfection/methods Transforming Growth Factor
beta/*genetics},
Abstract = {BACKGROUND: The objective of this study was to use a
chitosan-alginate gel to implant bone marrow-derived
mesenchymal stem cells subcutaneously in a minimally
invasive manner and promote bone formation by the
simultaneously transferred osteogenic protein (OP)-1 (bone
morphogenic protein-7) gene. METHOD AND RESULTS: The complex
of polyethylenimine/luciferase plasmid DNA embedded in the
gel was able to transfect HEK 293 cells on a culture dish or
co-encapsulated in the gel. When injected into the
subcutaneous space of mice, luciferase expression was two to
three orders of magnitude increased above the background. To
examine the efficacy of gene-, cell-, and combined gene- and
cell-encapsulated gels in tissue generation, samples were
injected into the subcutaneous space of 6-week-old athymic
nude mice, and the OP-1 plasmid was studied. At 8 weeks
after the injection, the gels only maintained their
volumetric shape when human mesenchymal stem cells (hMSCs)
were encapsulated, but otherwise the gels were partially
dissolved. Transgene expression of OP-1 was clearly detected
in the samples after 4 weeks but not after 8 weeks. Type II
collagen was detected in all the gels containing the OP-1
plasmid, with or without hMSCs. The samples with the
combination of OP-1 DNA and hMSCs revealed strong type II
collagen expression as well as osteoid foci. CONCLUSION:
These results suggest that combined gene and hMSC delivery
within a chitosan-alginate gel could be an interesting
approach for tissue engineering.},
Key = {Article}
}
@article{Article,
Author = {Tsurushima, H. and Yuan, X. and Dillehay, L. E. and Leong,
K. W.},
Title = {Radioresponsive tumor necrosis factor-related
apoptosisinducing ligand (TRAIL) gene therapy for malignant
brain tumors},
Journal = {Cancer Gene Therapy},
Volume = {14},
Number = {8},
Pages = {706-716},
Year = {2007},
Keywords = {radioresponsive gene therapy trail gene therapy the
combination with gene therapy and radiation therapy
malignant brain tumors in vivo electroporation
ionizing-radiation in-vivo glioma-cells hepatocellular-carcinoma
antitumor-activity egr-1 promoter induction receptor
electroporation activation},
Abstract = {Patients with malignant gliomas have a very poor prognosis.
To explore a novel and more effective approach for the
treatment of malignant gliomas, a strategy that combined
tumor necrosis factor-related apoptosis-inducing ligand
(TRAIL) gene therapy and radiation treatment (RT) was
designed in this study. Plasmid pE4- GFP was constructed by
including the radioinducible early growth response gene 1
(Egr-1) promoter, and it yielded the best response with
fractionated RT. Plasmid pE4- TRAIL was constructed by
including the Egr-1 promoter and evaluated using U251 and
U87 glioma cells. In the assay of apoptosis and killing
activities, pE4-TRAIL exhibited radioresponse. pE4-TRAIL
combined with RT is capable of inducing cell death
synergistically. The expression of TRAIL death receptors was
evaluated; which may be influenced by RT. Glioma cells with
wild- type p53 showed upregulated expression of death
receptors, and more synergistic effects on killing
activities are expected. pE4-TRAIL was transfected into the
subcutaneous U251 glioma cells in nude mice by the in vivo
electroporation method. In the mice treated with pE4- TRAIL
and RT, apoptotic cells were detected in pathological
sections, and a significant difference of tumor volumes was
observed when compared with the other groups (P <0.001). Our
results indicate that radioresponsive gene therapy may have
great potential as a novel therapy because this therapeutic
system can be spatially or temporally controlled by
exogenous RT and provides specificity and
safety.},
Key = {Article}
}
@article{Article,
Author = {Chai, C. and Leong, K. W.},
Title = {Biomaterials approach to expand and direct differentiation
of stem cells},
Journal = {Molecular Therapy},
Volume = {15},
Number = {3},
Pages = {467-480},
Year = {2007},
Keywords = {endothelial progenitor cells marrow stromal cells in-vitro
differentiation human adipose-tissue calcium-phosphate
ceramics corneal epithelial-cells primordial germ-cells
smooth-muscle-cells self-renewal chondrogenic
differentiation},
Abstract = {Stem cells play increasingly prominent roles in tissue
engineering and regenerative medicine. Pluripotent embryonic
stem (ES) cells theoretically allow every cell type in the
body to be regenerated. Adult stem cells have also been
identified and isolated from every major tissue and organ,
some possessing apparent pluripotency comparable to that of
ES cells. However, a major limitation in the translation of
stem cell technologies to clinical applications is the
supply of cells. Advances in biomaterials engineering and
scaffold fabrication enable the development of ex vivo cell
expansion systems to address this limitation. Progress in
biomaterial design has also allowed directed differentiation
of stem cells into specific lineages. In addition to
delivering biochemical cues, various technologies have been
developed to introduce micro- and nano-scale features onto
culture surfaces to enable the study of stem cell responses
to topographical cues. Knowledge gained from these studies
portends the alteration of stem cell fate in the absence of
biological factors, which would be valuable in the
engineering of complex organs comprising multiple cell
types. Biomaterials may also play an immunoprotective role
by minimizing host immunoreactivity toward transplanted
cells or engineered grafts.},
Key = {Article}
}
@article{Article,
Author = {Zhang, Y. and Chai, C. and Jiang, X. S. and Teoh, S. H. and Leong, K. W.},
Title = {Fibronectin immobilized by covalent conjugation or physical
adsorption shows different bioactivity on
aminated-PET},
Journal = {Materials Science & Engineering C-Biomimetic and
Supramolecular Systems},
Volume = {27},
Number = {2},
Pages = {213-219},
Year = {2007},
Keywords = {surface modification conjugation adsorption fibronectin
bioactivity extracellular-matrix proteins cell-adhesion
sulfate proteoglycan neurite outgrowth binding fragments
spinal-cord adult-rats surfaces integrins
growth},
Abstract = {To manipulate the cellular response to synthetic surfaces,
extracellular matrix (ECM) proteins such as fibronectin (FN)
and collagen are often immobilized on the surface to promote
interaction between these ligands and the cell receptors. In
this study we compared the biological properties of
FN-decorated polyethylene terephthalate (PET) produced by
two widely used immobilization techniques: adsorption and
conjugation. As revealed by the micro-bicinchoninic acid
(micro-BCA) assay and AFM, the modified surface topography
was dependent on the immobilization methods. Adsorption
method preserved the compact conformation of FN, reaching
saturation when a monolayer of FN was formed. Covalent
conjugation induced FN unfolding and fibrillogenesis,
forming multiple layers of FN. Biological characterization
by adhesion of baby hamster kidney 21 (BHK21) cells and
enzyme-linked immunosorbent assay (ELISA) for active
Arg-Gly-Asp (RGD) domains suggested that the difference in
conformation of FN led to different bioactivities.
Adsorption maintained a more active RGD domain, thereby
promoting cell adhesion, whereas conjugation induced
fibrillogenesis and blocked the access of RGD, consequently
suppressing cell adhesion as the surface density of FN
increased. This study suggests that in addition to choosing
the nature of the adhesion molecule, the mode of
immobilization may also significantly influence the
bioactivity of the surface. (c) 2006 Elsevier B.V. All
rights reserved.},
Key = {Article}
}
@article{Article,
Author = {Song, R. J. and Liu, S. Q. and Leong, K.
W.},
Title = {Effects of MIP-1 alpha, MIP-3 alpha, and MIP-3 beta on the
induction of HIV Gag-specific immune response with DNA
vaccines},
Journal = {Molecular Therapy},
Volume = {15},
Number = {5},
Pages = {1007-1015},
Year = {2007},
Keywords = {herpes-simplex-virus experimental autoimmune
encephalomyelitis inflammatory protein 3-alpha cc-chemokine
receptor dendritic cells expression plasmid t-lymphocytes
in-vivo gm-csf type-1},
Abstract = {Transfection of DNA vaccines with chemokines may recruit
dendritic cells (DCs) locally to capture the antigenic genes
and their gene products to generate enhanced CD8(+)
cytotoxic T lymphocytes (CTLs). In this study, we
investigated the effects of macrophage inflammatory protein
(MIP)-1 alpha, MIP-3 alpha, and MIP-3 beta on human
immunodeficiency virus (HIV) Gag DNA vaccination. The
chemokine plasmids markedly enhanced the local infiltration
of inflammatory cells and increased the presence of CD11c(+)
B7.2(+)-activated DCs. MIP-1 alpha and MIP-3 alpha were
potent adjuvants in augmenting CTLs and afforded strong
protection to immunized animals against challenge with
vaccinia virus expressing Gag (vv-Gag). However, decreased
humoral response was observed. MIP-3 beta plasmid did not
dramatically alter immunity. The chemokine inoculation time
with respect to DNA vaccine priming was also investigated.
The injection of pMIP-3 alpha three days before Gag plasmid
(pGag) vaccination markedly increased specific CTLs compared
with simultaneous injection and led to higher protection
against vv-Gag. Immunity was also shifted toward a T-helper
type-1(Th1) response. In contrast, inoculation with pMIP-3
alpha three days after pGag vaccination shifted immunity
toward a Th2 response. Our data suggest that administration
of a chemokine with DNA vaccines offers a valuable strategy
to modulate the efficacy and polarization of specific
immunity and that chemokine antigen timing is critical in
determining overall biological effects.},
Key = {Article}
}
@article{Article,
Author = {Yim, E. K. F. and Liao, I. C. and Leong, K.
W.},
Title = {Tissue compatibility of interfacial polyelectrolyte
complexation fibrous scaffold: Evaluation of blood
compatibility and biocompatibility},
Journal = {Tissue Engineering},
Volume = {13},
Number = {2},
Pages = {423-433},
Year = {2007},
Keywords = {mesenchymal stem-cells in-vitro controlled-release chitosan
alginate activation adhesion heparin fibers
films},
Abstract = {Interfacial polyelectrolyte complexation (PEC) fiber has
been proposed as a biostructural unit and biological
construct for tissue engineering applications, with its
ability to incorporate proteins, drug molecules, DNA
nanoparticles, and cells. In this study, we evaluated the
biocompatibility and blood compatibility of PEC fiber in
order to assess its potential for in vivo applications in
tissue engineering. Although chitosan-alginate PEC fibrous
scaffold was found to be thrombogenic, the blood
compatibility of the scaffold could be significantly
improved by incorporating a small amount of heparin in the
polyelectrolyte solution during fiber formation. The
platelet microparticle production and platelet adhesion on
the chitosan-alginate-heparin fibrous scaffold were
comparable to those on the resting control. In vitro
cytotoxicity test showed that the scaffold was not toxic to
human mesenchymal stem cells (hMSCs). In the in vivo
biocompatibility test in rats, no acute inflammation was
observed in the subcutaneously or intramuscularly implanted
specimens. Good cell infiltration and vascularization were
observed after 2 months of implantations. Enhanced
extracellular matrix (ECM) deposition was observed when
hMSCs were cultured in the transforming growth factor-beta 3
(TGF-beta 3)-encapsulated PEC fibrous scaffold in vitro, or
when the TGF-beta 3-encapsulated PEC was implanted
intramuscularly in vivo. The results showed that this
versatile PEC fibrous scaffold could be used in various
tissue engineering applications for its good biocompatible
and blood compatible properties.},
Key = {Article}
}
@article{Article,
Author = {Sharma, B. and Williams, C. G. and Kim, T. K. and Sun, D. N. and Malik, A. and Khan, M. and Leong, K. and Elisseeff, J.
H.},
Title = {Designing zonal organization into tissue-engineered
cartilage},
Journal = {Tissue Engineering},
Volume = {13},
Number = {2},
Pages = {405-414},
Year = {2007},
Keywords = {bovine articular-cartilage matrix production sub-populations
chondrocytes subpopulations networks morphology hydrogels
growth disc},
Abstract = {Cartilage tissue engineering strategies generally result in
homogeneous tissue structures with little resemblance to the
native zonal organization of articular cartilage. The
objective of this study was to use bilayered
photopolymerized hydrogels to organize zone-specific
chondrocytes in a stratified framework and study the effects
of this three-dimensional coculture system on the properties
of the engineered tissue. Superficial and deep zone
chondrocytes from bovine articular cartilage were
photoencapsulated in separate hydrogels as well as in
adjacent layers of a bilayered hydrogel. Histology,
mechanical testing, and biochemical analysis was performed
after culturing in vitro. To evaluate the influence of
coculture on tissue properties, the layers were separated
and compared to constructs containing only superficial or
deep cells. In the bilayered constructs, deep cells produced
more collagen and proteoglycan than superficial cells,
resulting in cartilage tissue with stratified, heterogeneous
properties. Deep cells cocultured with superficial cells in
the bilayered system demonstrated reduced proliferation and
increased matrix synthesis compared to deep cells cultured
alone. The bilayered constructs demonstrated greater shear
and compressive strength than homogenous cell constructs.
This study demonstrated that interactions between
zone-specific chondrocytes affect the biological and
mechanical properties of engineered cartilage. Strategies
aimed to structurally organize zone-specific cells and
encourage heterotypic cell interactions may contribute to
improved functional properties of engineered
cartilage.},
Key = {Article}
}
@article{Article,
Author = {Chua, K. N. and Tang, Y. N. and Quek, C. H. and Ramakrishna,
S. and Leong, K. W. and Mao, H. Q.},
Title = {A dual-functional fibrous scaffold enhances P450 activity of
cultured primary rat hepatocytes},
Journal = {Acta Biomaterialia},
Volume = {3},
Number = {5},
Pages = {643-650},
Year = {2007},
Keywords = {electrospun fiber surface modification drug encapsulation
hepatocyte culture 3-dimensional nanofibrous scaffold
mesenchymal stem-cells extracellular-matrix
organic-compounds electrospun solubility attachment
morphology spheroids induction},
Abstract = {We have designed a novel dual-functional electrospun fibrous
scaffold comprising two fiber mesh layers that were modified
differently to induce two separate biological responses from
hepatocytes. The first fiber layer was galactosylated on the
surface to mediate hepatocyte attachment, while the second
layer was loaded with 3-methylcholanthrene (3-Mc) to enhance
cytochrome P450 activity of hepatocytes. Primary rat
hepatocytes cultured on the galactosylated fibrous scaffolds
loaded with different concentrations of 3-Mc were compared
for their cell attachment efficiency, albumin secretion
activity and cytochrome P450-dependent 7-ethoxycoumarin
O-deethylase activity. This hybrid fibrous scaffold mediated
hepatocyte attachment with slightly lower efficiency (76 +/-
2.3%) than a single-layer galactosylated fibrous scaffold
(84 +/- 3.5%). More importantly, the cytochrome P450
activity of the hepatocytes cultured on the hybrid scaffold
correlated well with the 3-Mc loading level. The results
also showed that transfer of 3-Mc to hepatocytes through
direct cell-fiber contact was the dominant transport route,
with the induced cytochrome P450 activity being 1.9- to
4.8-fold higher than that of transfer of 3-Mc to hepatocytes
via dissolution from fibers to medium. This study
demonstrates the feasibility of creating multi-functional
fibrous scaffolds that serve both as an adhesive substrate
and as a delivery vehicle for bioactive molecules. (c) 2007
Acta Materialia Inc. Published by Elsevier Ltd. All rights
reserved.},
Key = {Article}
}
@article{Article,
Author = {Chua, K. N. and Chai, C. and Lee, P. C. and Ramakrishna, S. and Leong, K. W. and Mao, H. Q.},
Title = {Functional nanofiber scaffolds with different spacers
modulate adhesion and expansion of cryopreserved umbilical
cord blood hematopoietic stem/progenitor
cells},
Journal = {Experimental Hematology},
Volume = {35},
Number = {5},
Pages = {771-781},
Year = {2007},
Keywords = {ex-vivo expansion stem-cells progenitor cells cd34(+) cells
fibronectin culture transplantation immobilization
transduction engraftment},
Abstract = {Objective. Nanofiber scaffolds with amino groups conjugated
to fiber surface through different spacers (ethylene,
butylenes, and hexylene groups, respectively) were prepared
and the effect of spacer length on adhesion and expansion of
umbilical cord blood hematopoietic stem/progenitor cells
(HSPCs) was investigated. Materials and Methods. Electrospun
polymer nanofiber scaffolds were functionalized with
poly(acrylic acid) grafting, followed by conjugation of
amino groups with different spacers. HSPCs were expanded on
aminated scaffolds for 10 days. Cell proliferation, surface
marker expression, clonogenic potential, and nonobese
diabetic (NOD)/severe combined immunodeficient (SCID)
repopulation potential of the expanded cells were evaluated
following expansion culture. Results. Aminated nanofiber
scaffolds with ethylene and butylene spacers showed
high-expansion efficiencies (773- and 805-fold expansion of
total cells, 200- and 235-fold expansion of CD34(+)CD45(+)
cells, respectively). HSPC proliferation on aminated
scaffold with hexylene spacer was significantly lower
(210-fold expansion of total cells and 86-fold expansion of
CD34(+)CD45(+) cells), but maintained the highest
CD34(+)CD45(+) cell fraction (41.1%). Colony-forming unit
granulocyte-erythrocyte-monocyte-megakaryocyte and long-term
culture-initiating cell maintenance was similar for HSPCs
expanded on all three aminated nanofiber scaffolds;
nevertheless, the NOD/SCID mice engraftment potential of
HSPCs expanded on aminoethyl and aminobutyl conjugated
nanofibers was significantly higher than that on aminohexyl
conjugated nanofibers. Conclusion. This study demonstrated
that aminated nanofibers are superior substrates for ex vivo
HSPC expansion, which was correlated with the enhanced HSPC
adhesion to these aminated nanofibers. The spacer, through
which amino groups were conjugated to nanofiber surface,
affected the expansion outcome. Our results highlighted the
importance of scaffold topography and cell-substrate
interaction to regulating HSPC proliferation and
self-renewal in cytokine-supplemented expansion. (c) 2007
International Society for Experimental Hematology. Published
by Elsevier Inc.},
Key = {Article}
}
@article{Article,
Author = {Yim, E. K. F. and Pang, S. W. and Leong, K.
W.},
Title = {Synthetic nanostructures inducing differentiation of human
mesenchymal stem cells into neuronal lineage},
Journal = {Experimental Cell Research},
Volume = {313},
Number = {9},
Pages = {1820-1829},
Year = {2007},
Keywords = {nanotopography human mesenchymal stem cells neuronal
differentiation nanoimprinting cytoskeleton rearrangement
marrow stromal cells polymer-demixed nanotopography in-vitro
differentiation surface-features neural cells topography
expression morphology phenotype nucleus},
Abstract = {Human mesenchymal stem cells (hMSCs) have been shown to
trans-differentiate into neuronal-like cells by culture in
neuronal induction media, although the mechanism is not well
understood. Topography can also influence cellular responses
including enhanced differentiation of progenitor cells. As
extracellular matrix (ECM) in vivo comprises topography in
the nanoscale, we hypothesize that nanotopography could
influence stem cell differentiation into specific
non-default pathways, such as transdifferentiation of hMSCs.
Differentiation and proliferation of hMSCs were studied on
nanogratings of 350 nm width. Cytoskeleton and nuclei of
hMSCs were aligned and elongated along the nanogratings.
Gene profiling and immunostaining showed significant
up-regulation of neuronal markers such as
microtubule-associated protein 2 (MAP2) compared to
unpatterned and micropatterned controls. The combination of
nanotopography and biochemical cues such as retinoic acid
further enhanced the up-regulation of neuronal marker
expressions, but nanotopography showed a stronger effect
compared to retinoic acid alone on unpatterned surface. This
study demonstrated the significance of nanotopography in
directing differentiation of adult stem cells. (c) 2007
Elsevier Inc. All rights reserved.},
Key = {Article}
}
@article{Article,
Author = {Chew, S. Y. and Mi, R. F. and Hoke, A. and Leong, K.
W.},
Title = {Aligned protein-polymer composite fibers enhance nerve
regeneration: A potential tissue-engineering
platform},
Journal = {Advanced Functional Materials},
Volume = {17},
Number = {8},
Pages = {1288-1296},
Year = {2007},
Keywords = {3-dimensional nanofibrous scaffold mesenchymal stem-cells
rat sciatic-nerve schwann-cells neurotrophic factors
peripheral-nerves delivery release filaments
grafts},
Abstract = {Sustained release of proteins from aligned polymeric fibers
holds great potential in tissue-engineering applications.
These protein-polymer composite fibers possess high
surface-area-to-volume ratios for cell attachment, and can
provide biochemical and topographic cues to enhance tissue
regeneration. Aligned biodegradable polymeric fibers that
encapsulate human glial cell-derived neurotrophic factor
(GDNF, 0.13 wt%) were fabricated via electrospinning a
copolymer of caprolactone and ethyl ethylene phosphate
(PCLEEP) with GDNF. The protein was randomly dispersed
throughout the polymer matrix in aggregate form, and
released in a sustained manner for up to two months. The
efficacy of these composite fibers was tested in a rat model
for peripheral nerve-injury treatment. Rats were divided
into four groups, receiving either empty PCLEEP tubes
(control); 1 tubes with plain PCLEEP electrospun. fibers
aligned longitudinally (EF-L) or circumferentially (EF-C);
or tubes with aligned GDNF-PCLEEP fibers (EF-L-GDNF). After
three months, bridging of a 15 mm critical defect gap by the
regenerated nerve was observed in all the rats that received
nerve conduits with electrospun fibers, as opposed to 50% in
the control group. Electrophysiological recovery was seen in
20%, 33%, and 44% of the rats in the EF-C, EF-L, and
EF-L-GDNF groups respectively, whilst none was observed in
the controls. This study has demonstrated that, without
further modification, plain electrospun fibers can help in
peripheral nerve regeneration; however, the synergistic
effect of an encapsulated growth factor facilitated a more
significant recovery. This study also demonstrated the novel
use of electrospinning to incorporate biochemical and
topographical cues into a single implant for in vivo
tissue-engineering applications.},
Key = {Article}
}
@article{Article,
Author = {Tsurushima, H. and Yuan, X. and Dillehay, L. E. and Leong,
K. W.},
Title = {Radio-responsive gene therapy for malignant glioma cells
without the radiosensitive promoter: Caspase-3 gene therapy
combined with radiation},
Journal = {Cancer Letters},
Volume = {246},
Number = {1-2},
Pages = {318-323},
Year = {2007},
Keywords = {caspase-3 gene therapy radio-responsive gene therapy
radiation radiation-sensitive promoter wild-type p53
adenovirus-mediated transfer thymidine kinase gene in-vivo
ionizing-radiation transgene expression egr-1 promoter death
activation ganciclovir},
Abstract = {Caspase-3 plays a critical role as an executioner of
apoptosis. The aim of this study is to evaluate the
potential of the combination of caspase-3 gene therapy and
radiation treatment. We prepared a plasmid (pCI-CSP3) that
contained the human caspase-3 gene and the cytomegalovirus
promoter. We introduced this plasmid into U251 and U87 human
glioma cells and subjected the cells to radiation treatment.
The degree of cell death and apoptosis were evaluated. None
of the cell lines underwent apoptosis by the overexpression
of caspase-3 alone, but the degree of cell death and
apoptosis were markedly enhanced by the addition of
radiation treatment. Next, we prepared another plasmid
(EGR-CSP3) that contained the caspase-3 gene and a
radiation-sensitive promoter. Each treatment system using
either pCI-CSP3 or EGR-CSP3 showed radio response. The
treatment system using pCI-CSP3 more effectively induced
apoptosis than that using EGR-CSP3. Caspase-3 gene therapy
in combination with radiation treatment has the potential to
serve as a radio-responsive gene therapy without any
radiation-sensitive promoter. (c) 2006 Elsevier Ireland Ltd.
All rights reserved.},
Key = {Article}
}
@article{Article,
Author = {Dang, J.M. and Leong, K. W.},
Title = {Myogenic induction of aligned mesenchymal stem cell sheets
by culture on thermally responsive electrospun
nanofibers},
Journal = {Advanced Materials},
Volume = {19},
Number = {19},
Pages = {2775-2779},
Year = {2007},
Key = {Article}
}
@article{Article,
Author = {Dai, H. and Jiang, X. and Tan, G. C. and Chen, Y. and Torbenson, M. and Leong, K. W. and Mao, H.
Q.},
Title = {Chitosan-DNA nanoparticles delivered by intrabiliary
infusion enhance liver-targeted gene delivery},
Journal = {International Journal of Nanomedicine},
Volume = {1},
Number = {4},
Pages = {507-522},
Year = {2006},
Keywords = {nanoparticles gene delivery liver-targeted chitosan
retrograde intrabiliary infusion water-soluble chitosan
naked plasmid DNA rat biliary-tract in-vivo bile-duct
transfection efficiency cytokine production cationic
liposomes nonviral vectors portal-vein},
Abstract = {The goal of this study was to examine the efficacy of
liver-targeted gene delivery by chitosan-DNA nanoparticles
through retrograde intrabiliary infusion (RII). The
transfection efficiency of chitosan-DNA nanoparticles, as
compared with PEI-DNA nanoparticles or naked DNA, was
evaluated in Wistar rats by infusion into the common bile
duct, portal vein, or tail vein. Chitosan-DNA nanoparticles
administrated through the portal vein or tail vein did not
produce detectable luciferase expression. In contrast, rats
that received chitosan-DNA nanoparticles showed more than
500 times higher luciferase expression in the liver 3 days
after RII; and transgene expression levels decreased
gradually over 14 days. Luciferase expression in the kidney,
lung, spleen, and heart was negligible compared with that in
the liver. R-II of chitosan-DNA nanoparticles did not yield
significant toxicity and damage to the liver and biliary
tree as evidenced by liver function analysis and
histopathological examination. Luciferase expression by RII
of PEI-DNA nanoparticles was 17-fold lower than that of
chitosan-DNA nanoparticles on day 3, but it increased
slightly over time. These results suggest that RII is a
promising routine to achieve liver-targeted gene delivery by
non-viral nanoparticles; and both gene carrier
characteristics and mode of administration significantly
influence gene delivery efficiency.},
Key = {Article}
}
@article{Article,
Author = {Le Visage and C. and Kim, S. W. and Tateno, K. and Sieber, A.
N. and Kostuik, J. P. and Leong, K. W.},
Title = {Interaction of human mesenchymal stem cells with disc cells
- Changes in extracellular matrix biosynthesis},
Journal = {Spine},
Volume = {31},
Number = {18},
Pages = {2036-2042},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Ong, S. Y. and Dai, H. and Leong, K. W.},
Title = {Inducing hepatic differentiation of human mesenchymal stem
cells in pellet culture},
Journal = {Biomaterials},
Volume = {27},
Number = {22},
Pages = {4087-4097},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Bright, C. and Park, Y. S. and Sieber, A. N. and Kostuik, J.
P. and Leong, K. W.},
Title = {In vivo evaluation of plasmid DNA encoding OP-1 protein for
spine fusion},
Journal = {Spine},
Volume = {31},
Number = {19},
Pages = {2163-2172},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Yim, E. K. and Wan, A. C. and Le Visage and C. and Liao, I. C. and Leong, K. W.},
Title = {Proliferation and differentiation of human mesenchymal stem
cell encapsulated in polyelectrolyte complexation fibrous
scaffold},
Journal = {Biomaterials},
Volume = {27},
Number = {36},
Pages = {6111-22},
Year = {2006},
Abstract = {A biofunctional scaffold was constructed with human
mesenchymal stem cells (hMSCs) encapsulated in
polyelectrolyte complexation (PEC) fibers. Human MSCs were
either encapsulated in PEC fibers and constructed into a
fibrous scaffold or seeded on PEC fibrous scaffolds. The
proliferation, chondrogenic and osteogenic differentiation
of the encapsulated and seeded hMSCs were compared for a
culture period of 5.5 weeks. Gene expression and
extracellular matrix production showed evidences of
chondrogenesis and osteogenesis in the cell-encapsulated
scaffolds and cell-seeded scaffolds when the samples were
cultured in the chondrogenic and osteogenic differentiation
media, respectively. However, better cell proliferation and
differentiation were observed on the hMSC-encapsulated
scaffolds compared to the hMSC-seeded scaffolds. The study
demonstrated that the cell-encapsulated PEC fibers could
support proliferation and chondrogenic and osteogenic
differentiation of the encapsulated-hMSCs. Together with our
previous works, which demonstrated the feasibility of PEC
fiber in controlled release of drug, protein and gene
delivery, the reported PEC fibrous scaffold system will have
the potential in composing a multi-component system for
various tissue-engineering applications.},
Key = {Article}
}
@article{Article,
Author = {Luong-Van, E. and Grondahl, L. and Chua, K. N. and Leong, K.
W. and Nurcombe, V. and Cool, S. M.},
Title = {Controlled release of heparin from poly(epsilon-caprolactone)
electrospun fibers},
Journal = {Biomaterials},
Volume = {27},
Number = {9},
Pages = {2042-2050},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Dang, J. M. and Leong, K. W.},
Title = {Natural polymers for gene delivery and tissue
engineering},
Journal = {Advanced Drug Delivery Reviews},
Volume = {58},
Number = {4},
Pages = {487-499},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Li, J. and Li, X. and Ni, X. P. and Wang, X. and Li, H. Z. and Leong, K. W.},
Title = {Self-assembled supramolecular hydrogels formed by
biodegradable PEO-PHB-PEO triblock copolymers and
alpha-cyclodextrin for controlled drug delivery},
Journal = {Biomaterials},
Volume = {27},
Number = {22},
Pages = {4132-4140},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Yim, E. K. F. and Wen, J. and Leong, K. W.},
Title = {Enhanced extracellular matrix production and differentiation
of human embryonic germ cell derivatives in biodegradable
poly(epsilon-caprolactone-co-ethyl ethylene phosphate)
scaffold},
Journal = {Acta Biomaterialia},
Volume = {2},
Number = {4},
Pages = {365-376},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Chew, S. Y. and Hufnagel, T. C. and Lim, C. T. and Leong, K.
W.},
Title = {Mechanical properties of single electrospun
drug-encapsulated nanofibres},
Journal = {Nanotechnology},
Volume = {17},
Number = {15},
Pages = {3880-3891},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Zhang, Y. and Chai, C. and Jiang, X. S. and Teoh, S. H. and Leong, K. W.},
Title = {Co-culture of umbilical cord blood CD34(+) cells with human
mesenchymal stem cells},
Journal = {Tissue Engineering},
Volume = {12},
Number = {8},
Pages = {2161-2170},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Chen, H. H. and Leong, K. W.},
Title = {Quantum-dots-FRET nanosensors for detecting unamplified
nucleic acids by single molecule detection},
Journal = {Nanomedicine},
Volume = {1},
Number = {1},
Pages = {119-122},
Year = {2006},
Keywords = {confocal fluorescence spectroscopy fluorescence resonance
energy transfer (fret) nanosensor nucleic acids
oligonucleotide ligation assay quantum dot single molecuule
detection resonance energy-transfer DNA donors},
Abstract = {Quantitative and sensitive detection of minute copies of
nucleic acid sequences is critical in diagnosing disease and
in understanding biomolecular processes. An
inorganic-organic hybrid fluorescence resonance energy
transfer (FRET) nanosensor based on quantum dots (QDs) was
developed to overcome the limitations of conventional
FRET-based probes. Functionalized QDs served as FRET donors
and as nanoassemblies that can couple to multiple targets
hybridized as a sandwich between a capture probe and a
reporter probe. Target sequences are detected directly in
solution by single molecule detection (SMD) without prior
separation or amplification. This system is sensitive enough
to detect approximately 50 or fewer copies and to
discriminate point mutations. QD-FRET and SMD are platform
technologies that will find many applications for detecting
biomarkers or studying various biomolecules in a highly
sensitive and quantitative manner.},
Key = {Article}
}
@article{Article,
Author = {Wu, D. C. and Liu, Y. and Jiang, X. and He, C. B. and Goh,
S. H. and Leong, K. W.},
Title = {Hyperbranched poly(amino ester)s with different terminal
amine groups for DNA delivery},
Journal = {Biomacromolecules},
Volume = {7},
Number = {6},
Pages = {1879-1883},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Li, Q. and Wang, J. and Shahani, S. and Sun, D. D. N. and Sharma, B. and Elisseeff, J. H. and Leong, K.
W.},
Title = {Biodegradable and photocrosslinkable polyphosphoester
hydrogel},
Journal = {Biomaterials},
Volume = {27},
Number = {7},
Pages = {1027-1034},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Bowman, K. and Leong, K. W.},
Title = {Chitosan nanoparticles for oral drug and gene
delivery},
Journal = {International Journal of Nanomedicine},
Volume = {1},
Number = {2},
Pages = {117-128},
Year = {2006},
Keywords = {chitosan oral delivery nanoparticles in-vitro evaluation
poorly absorbable drugs peroral peptide delivery
epithelial-cells caco-2 DNA nanoparticles molecular-weight
intestinal-absorption transfection efficiency biodegradable
microparticles mucoadhesive properties},
Abstract = {Chitosan is a widely available, mucoadhesive polymer that is
able to increase cellular permeability and improve the
bioavailability of orally administered protein drugs. It can
also be readily formed into nanoparticles able to entrap
drugs or condense plasmid DNA. Studies on the formulation
and oral delivery of such chitosan nanoparticles have
demonstrated their efficacy in enhancing drug uptake and
promoting gene expression. This review summarizes some of
these findings and highlights the potential of chitosan as a
component of oral delivery systems.},
Key = {Article}
}
@article{Article,
Author = {Jiang, X. S. and Chai, C. and Zhang, Y. and Zhuo, R. X. and Mao, H. Q. and Leong, K. W.},
Title = {Surface-immobilization of adhesion peptides on substrate for
ex vivo expansion of cryopreserved umbilical cord blood
CD34(+) cells},
Journal = {Biomaterials},
Volume = {27},
Number = {13},
Pages = {2723-2732},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Tsurushima, H. and Yoshii, Y. and Leong, K. and Ohno,
T.},
Title = {Targeted tumor cell death induced by autologous
tumor-specific T lymphocyte recognition of wild-type
p53-derived peptides},
Journal = {Journal of Neuro-Oncology},
Volume = {76},
Number = {2},
Pages = {99-104},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Lim, S. H. and Liao, I. C. and Leong, K.
W.},
Title = {Nonviral gene delivery from nonwoven fibrous scaffolds
fabricated by interfacial complexation of
polyelectrolytes},
Journal = {Molecular Therapy},
Volume = {13},
Number = {6},
Pages = {1163-1172},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Song, R. J. and Liu, S. Q. and Adams, R. J. and Leong, K.
W.},
Title = {Enhancing efficacy of HIV Gag DNA vaccine by local delivery
of GM-CSF in murine and macaque models},
Journal = {Journal of Interferon and Cytokine Research},
Volume = {26},
Number = {6},
Pages = {380-389},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Dang, J. M. and Sun, D. D. N. and Shin-Ya, Y. and Sieber, A.
N. and Kostuik, J. P. and Leong, K. W.},
Title = {Temperature-responsive hydroxybutyl chitosan for the culture
of mesenchymal stem cells and intervertebral disk
cells},
Journal = {Biomaterials},
Volume = {27},
Number = {3},
Pages = {406-418},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Jiang, X. and Dai, H. and Leong, K. W. and Goh, S. H. and Mao, H. Q. and Yang, Y. Y.},
Title = {Chitosan-g-PEG/DNA complexes deliver gene to the rat liver
via intrabiliary and intraportal infusions},
Journal = {Journal of Gene Medicine},
Volume = {8},
Number = {4},
Pages = {477-487},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Li, J. and Yang, C. and Li, H. Z. and Wang, X. and Goh, S.
H. and Ding, J. L. and Wang, D. Y. and Leong, K.
W.},
Title = {Cationic supramolecules composed of multiple
oligoethylenimine-grafted beta-cyclodextrins threaded on a
polymer chain for efficient gene delivery},
Journal = {Advanced Materials},
Volume = {18},
Number = {22},
Pages = {2969-2974},
Year = {2006},
Keywords = {alpha-cyclodextrin polyamidoamine dendrimer conjugated
polyrotaxanes inclusion complexation drug-delivery
side-chain in-vivo therapy polypseudorotaxanes
polyethylenimine},
Abstract = {Cationic supramolecules composed of mumple
oligoethylenimine-grafted beta-cyclodextrins that are
threaded and blocked on a triblock copolymer chain (see
figure) are synthesized as gene-delivery vectors. The
supramolecules contain many cationic cyclic units threaded
on a polymer chain to form an integrated entity, functioning
as a macromolecular gene vector with good DNA binding
ability, low cytotoxicity, and high gene-transfection
efficiency.},
Key = {Article}
}
@article{Article,
Author = {Le Visage and C. and Yang, S. H. and Kadakia, L. and Sieber, A.
N. and Kostuik, J. P. and Leong, K. W.},
Title = {Small intestinal submucosa as a potential bioscaffold for
intervertebral disc regeneration},
Journal = {Spine},
Volume = {31},
Number = {21},
Pages = {2423-2430},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Chew, S. Y. and Wen, Y. and Dzenis, Y. and Leong, K.
W.},
Title = {The role of electrospinning in the emerging field of
nanomedicine},
Journal = {Current Pharmaceutical Design},
Volume = {12},
Number = {36},
Pages = {4751-4770},
Year = {2006},
Keywords = {bombyx-mori silk 3-dimensional nanofibrous scaffold normal
human keratinocytes mesenchymal stem-cells
smooth-muscle-cells collagen type-ii in-vitro poly(ethylene
oxide) fiber formation mechanical-properties},
Abstract = {The fact that in vivo the extracellular matrix (ECM) or
substratum with which cells interact often includes
topography at the nanoscale underscores the importance of
investigating cell-substrate interactions and performing
cell culture at the submicron scale. An important and
exciting direction of research in nanomedicine would be to
gain an understanding and exploit the cellular response to
nanostructures. Electrospinning is a simple and versatile
technique that can produce a macroporous scaffold comprising
randomly oriented or aligned nanofibers. It can also
accommodate the incorporation of drug delivery function into
the fibrous scaffold. Endowed with both topographical and
biochemical signals such electrospun nanofibrous scaffolds
may provide an optimal microenvironment for the seeded
cells. This review covers the analysis and control of the
electrospinning process, and describes the types of
electrospun fibers fabricated for biomedical applications
such as drug delivery and tissue engineering.},
Key = {Article}
}
@article{Article,
Author = {Chua, K. N. and Chai, C. and Lee, P. C. and Tang, Y. N. and Ramakrishna, S. and Leong, K. W. and Mao, H.
Q.},
Title = {Surface-aminated electrospun nanofibers enhance adhesion and
expansion of human umbilical cord blood hematopoietic
stem/progenitor cells},
Journal = {Biomaterials},
Volume = {27},
Number = {36},
Pages = {6043-51},
Year = {2006},
Abstract = {Interaction between hematopoietic stem/progenitor cells
(HSPCs) and their extra cellular matrix components is an
integral part of the signaling control for HSPC survival,
proliferation and differentiation. We hypothesized that both
substrate topographical cues and biochemical cues could act
synergistically with cytokine supplementation to improve ex
vivo expansion of HSPCs. In this study, we compared the ex
vivo expansion of human umbilical cord blood CD34(+) cells
on unmodified, hydroxylated, carboxylated and aminated
nanofibers and films. Results from 10-day expansion cultures
showed that aminated nanofiber mesh and film were most
efficient in supporting the expansion of the CD34(+)CD45(+)
cells (195-fold and 178-fold, respectively), as compared to
tissue culture polystyrene (50-fold, p<0.05). In particular,
aminated nanofiber meshes supported a higher degree of cell
adhesion and percentage of HSPCs, as compared to aminated
films. SEM imaging revealed the discrete colonies of cells
proliferating and interacting with the aminated nanofibers.
This study highlights the potential of a biomaterials
approach to influence the proliferation and differentiation
of HSPCs ex vivo.},
Key = {Article}
}
@article{Article,
Author = {Feng, Q. and Chai, C. and Jiang, X. S. and Leong, K. W. and Mao, H. Q.},
Title = {Expansion of engrafting human hematopoietic stem/progenitor
cells in three-dimensional scaffolds with
surface-immobilized fibronectin},
Journal = {Journal of Biomedical Materials Research Part
A},
Volume = {78A},
Number = {4},
Pages = {781-791},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Wong, K. and Sun, G. B. and Zhang, X. Q. and Dai, H. and Liu, Y. and He, C. B. and Leong, K. W.},
Title = {PEI-g-chitosan, a novel gene delivery system with
transfection efficiency comparable to polyethylenimine in
vitro and after liver administration in vivo},
Journal = {Bioconjugate Chemistry},
Volume = {17},
Number = {1},
Pages = {152-158},
Year = {2006},
Key = {Article}
}
@article{Article,
Author = {Ho, Y. P. and Chen, H. H. and Leong, K. W. and Wang, T.
H.},
Title = {Evaluating the intracellular stability and unpacking of DNA
nanocomplexes by quantum dots-FRET},
Journal = {J Control Release},
Volume = {116},
Number = {1},
Pages = {83-9},
Year = {2006},
Abstract = {We demonstrate a highly sensitive method to characterize the
structural composition and intracellular fate of polymeric
DNA nanocomplexes, formed by condensing plasmid DNA with
cationic polymers through electrostatic interactions.
Rational design of more efficient polymeric gene carriers
will be possible only with mechanistic insights of the
rate-limiting steps in the non-viral gene transfer process.
To characterize the composition and binding dynamics of
nanocomplexes, plasmid and its polymer carrier within
nanocomplexes were labeled with quantum dots (QDs) and
fluorescent organic dyes, respectively, as a donor and
acceptor pair for fluorescence resonance energy transfer
(FRET). The high signal-to-noise ratio in QD-mediated FRET
enabled precise detection of discrete changes in nanocomplex
state at the single-particle level, against various
intracellular microenvironments. The distribution and
unpacking of individual nanocomplexes within cells could
thus be unambiguously followed by fluorescence microscopy.
QD-FRET is a highly sensitive and quantitative method to
determine the composition and dynamic stability of
nanocomplexes during intracellular transport, where barriers
to gene delivery may be identified to facilitate gene
carrier optimization.},
Key = {Article}
}
@article{Article,
Author = {Li, X. and Mya, K. Y. and Ni, X. P. and He, C. B. and Leong,
K. W. and Li, J.},
Title = {Dynamic and static light scattering studies on
self-aggregation behavior of biodegradable amphiphilic
poly(ethylene oxide)-poly [(R)-3-hydroxybutyrate]-poly(ethylene
oxide) triblock copolymers in aqueous solution},
Journal = {Journal of Physical Chemistry B},
Volume = {110},
Number = {12},
Pages = {5920-5926},
Year = {2006},
Key = {Article}
}
@article{05329287121,
Author = {Liu, Ye and Wu, De-Cheng and Zhang, Wei-De and Jiang, Xuan and He, Chao-Bin and Chung, Tai Shung and Goh, Suat Hong and Leong, Kam W.},
Title = {Polyethylenimine-grafted multiwalled carbon nanotubes for
secure noncovalent immobilization and efficient delivery of
DNA},
Journal = {Angewandte Chemie - International Edition},
Volume = {44},
Number = {30},
Pages = {4782 - 4785},
Year = {2005},
url = {http://dx.doi.org/10.1002/anie.200500042},
Keywords = {Organic polymers;Grafting (chemical);DNA;Electrostatics;},
Abstract = {(Figure Presented) DNA hits the wall: DNA is immobilized
securely onto the surface of multiwalled carbon nanotubes
through electrostatic interactions with grafted
polyethylenimine (PEI; see picture). The
polyethylenimine-graft multiwalled carbon nanotubes carrying
DNA show transfection efficiency for DNA delivery similar to
or even several times higher than PEI. © 2005 Wiley-VCH
Verlag GmbH and Co. KGaA.},
Key = {05329287121}
}
@article{Article,
Author = {Lu, H. F. and Lim, W. S. and Zhang, P. C. and Chia, S. M. and Yu, H. and Mao, H. Q. and Leong, K. W.},
Title = {Galactosylated poly(vinylidene difluoride) hollow fiber
bioreactor for hepatocyte culture},
Journal = {Tissue Engineering},
Volume = {11},
Number = {11-12},
Pages = {1667-1677},
Year = {2005},
Key = {Article}
}
@article{05068830381,
Author = {Zhang, Xue-Qing and Wang, Xu-Li and Zhang, Peng-Chi and Liu,
Zhi-Lan and Zhuo, Ren-Xi and Mao, Hai-Quan and Leong, Kam
W.},
Title = {Galactosylated ternary DNA/polyphosphoramidate nanoparticles
mediate high gene transfection efficiency in
hepatocytes},
Journal = {Journal of Controlled Release},
Volume = {102},
Number = {3},
Pages = {749 - 763},
Year = {2005},
url = {http://dx.doi.org/10.1016/j.jconrel.2004.10.024},
Keywords = {Gene transfer;DNA;Bioassay;Cells;Gels;Synthesis
(chemical);Optimization;},
Abstract = {Galactosylated polyphosphoramidates (Gal-PPAs) with
different ligand substitution degrees (6.5%, 12.5% and
21.8%, respectively) were synthesized and evaluated as
hepatocyte-targeted gene carriers. The in vitro cytotoxicity
of Gal-PPA decreased significantly with an increase in
galactose substitution degree. The affinity of Gal-PPA/DNA
nanoparticles to galactose-recognizing lectin increased with
galactose substitution degree. However, decreased
transfection efficiency was observed for these
galactosylated PPAs in HepG2 cells. Based on the results of
gel retardation and polyanion competition assays, we
hypothesized that the reduced transfection efficiency of
Gal-PPA/DNA nanoparticles was due to their decreased
DNA-binding capacity and decreased particle stability. We
therefore prepared nanoparticles by precondensing DNA with
PPA at a charge ratio of 0.5, yielding nanoparticles with
negative surface charge, followed by coating with Gal-PPA,
resulting in a Gal-PPA/ DNA/PPA ternary complex. Such a
ternary nanoparticle formulation led to significant size
reduction in comparison with binary nanoparticles,
particularly at low N/P ratios (2 to 5). In HepG2 cells and
primary rat hepatocytes, and at low N/P ratios (2 to 5),
transfection efficiency mediated by ternary nanoparticles
prepared with 6.5% Gal-PPA was 6-7200 times higher than
PPA-DPA/DNA nanoparticles. Transgene expression increased
slightly at higher N/P ratios in HepG2 cells and reached a
plateau at N/P ratios between 5 and 10 for primary rat
hepatocytes. Such an enhancement effect was not observed in
HeLa cells that lack of asialoglycoprotein receptor (ASGPR).
Nevertheless, transfection efficiency of ternary particles
decreased dramatically, presumably due to the decreased DNA
binding capacity and particle stability, as PPA
galactosylation degree increased. This highlights the
importance of optimizing ligand conjugation degree for PPA
gene carrier. © 2004 Elsevier B.V. All rights
reserved.},
Key = {05068830381}
}
@article{06239927940,
Author = {Leong, Kam W.},
Title = {Polymeric controlled nucleic acid delivery},
Journal = {MRS Bulletin},
Volume = {30},
Number = {9},
Pages = {640 - 646},
Year = {2005},
Keywords = {Polymers;Gene transfer;Nanostructured materials;Biomaterials;Nanotechnology;},
Abstract = {Gene therapy harbors great promise for the treatment of a
variety of inherited and acquired diseases, but its
potential can be realized only with safe and effective
carriers. Although viruses can efficiently transfer foreign
genes to cells, their long-term safety remains a concern.
Polymers can serve as a carrier to facilitate gene transfer,
either by condensing DNA to the size of nanoparticles that
can be internalized by cells, or by entrapping DNA in
matrices or micro/nanoparticles for sustained release.
However, polymeric controlled gene delivery remains highly
inefficient. This review covers the major barriers for
nonviral gene transfer and briefly describes the different
types of polymers developed to overcome these barriers. With
the tremendous promise of genetic medicine, nonviral gene
delivery is a worthy goal for biomaterials and
nanotechnology research.},
Key = {06239927940}
}
@article{05108867763,
Author = {Zhang, Xue-Qing and Wang, Xu-Li and Huang, Shi-Wen and Zhuo,
Ren-Xi and Liu, Zhi-Lan and Mao, Hai-Quan and Leong, Kam
W.},
Title = {In vitro gene delivery using polyamidoamine dendrimers with
a trimesyl core},
Journal = {Biomacromolecules},
Volume = {6},
Number = {1},
Pages = {341 - 350},
Year = {2005},
url = {http://dx.doi.org/10.1021/bm040060n},
Keywords = {Biomaterials;Genes;Structure (composition);DNA;Bioassay;Toxicity;pH
effects;Amino acids;},
Abstract = {Polyamidoamine (PAMAM) dendrimer represents one of the most
efficient polymeric gene carriers. To investigate the effect
of the core structure and generation of dendrimers on the
complex formation and transfection efficiency, a series of
PAMAM dendrimers with a trimesyl core (DT) at different
generations (DT4 to DT8) were developed as gene carriers and
compared with the PAMAM dendrimers derived from
pentaerythritol (DP) and inositol (DI). The minimal
generation number of DTs at which the dendrimer has enough
amino group density to effectively condense DNA was higher
(generation 6) than those of DPs and DIs (generation 5). DTs
of generation 6 or higher condensed DNA into complexes with
an average diameter ranging from 100 to 300 nm, but the 4th
and 5th generations of DT (DT4 and DT5) formed only a severe
aggregate with DNA. Interestingly, the DT6/pDNA complex was
determined to be much smaller (100-300 nm) than those
prepared with DP5 or D15 (>600 nm) at N/P ratios higher
than 15. The optimal generation numbers at which the
dendrimers showed the highest transgene expression in COS-7
cells were 5 for DPs and DIs but 6 for DTs. The
DT6/pDNAcomplex with smaller size mediated higher transgene
expression in COS-7 cells than those prepared with DP5 or
D15. The in vitro transfection efficiency of the DT
dendrimers as evaluated in HeLa cells, COS-7 cells, and
primary hepatocytes decreased in the order of DT6 > DT7
> DT8 > DT5 > DT4. The transfection mediated by DT6
was significantly inhibited by bafilomycin A1. The acid-base
titration curve for DT6 showed high buffer capacity in the
pH range from 5.5 to 6.4 (pK<sub>a</sub> approximately
equals 6). This permits dendrimers to buffer the pH change
in the endosomal compartment. However, the transfection
efficiency mediated by DT6 decreased significantly in the
presence of serum in both HeLa cells and COS-7 cells. The
cytotoxicity of DTs evaluated in HeLa cells using the
3-{4,5-dimethylthiazol-2-yl}-2,5-diphenyltetrazolium bromide
assay showed a trend of increasing toxicity with the polymer
generations. The LD50 values of DT4 through DT8 were 628,
236, 79, 82, and 77 μg/mL, respectively, which were
higher than that of poly(ethyleneimide) (18 μg/mL) and
poly(L-lysine) (28 μg/mL) in the same assay. With a lower
cytotoxicity and versatility for chemical conjugation, these
PAMAM dendrimers with a DT core warrant further
investigation for nonviral gene delivery. © 2005
American Chemical Society.},
Key = {05108867763}
}
@article{05329287024,
Author = {Chia, Ser-Mien and Lin, Pao-Chun and Quek, Chai-Hoon and Yin, Chao and Mao, Hai-Quan and Leong, Kam W. and Xu, Xi and Goh, Cho-Hong and Ng, Mah-Lee and Yu, Hanry},
Title = {Engineering microenvironment for expansion of sensitive
anchorage-dependent mammalian cells},
Journal = {Journal of Biotechnology},
Volume = {118},
Number = {4},
Pages = {434 - 447},
Year = {2005},
url = {http://dx.doi.org/10.1016/j.jbiotec.2005.05.012},
Keywords = {Tissue;Collagen;Positive ions;Cell culture;Polymers;Fibers;Enzymes;},
Abstract = {Tissue engineering involves ex vivo seeding of
anchorage-dependent mammalian cells onto scaffolds, or
transplanting cells in vivo. The cell expansion currently
requires repeated cell detachment from solid substrata by
enzymatic, chemical or mechanical means. The report here
presents a high yield three-dimensional culture and harvest
system circumventing the conventional detachment
requirements. Cells mixed with dilute cationic collagen were
microencapsulated within an ultra-thin shell of synthetic
polymers. The cationic collagen could rapidly form a
conformal layer of collagen fibers around cells to support
cell proliferation and functions. The collagen could be
readily removed from cells with a buffer rinse after
harvesting from the fragile microcapsules. The cells
harvested from this system demonstrate improved attachment,
morphology and functions over conventionally cultured cells,
upon binding to ligand-conjugated polymer surfaces. The
harvested cells can be re-encapsulated and allowed to
proliferate again, or used immediately in applications.
© 2005 Elsevier B.V. All rights reserved.},
Key = {05329287024}
}
@article{Article,
Author = {Zhang, X. Q. and Wang, X. L. and Huang, S. W. and Zhuo, R.
X. and Liu, Z. L. and Mao, H. Q. and Leong, K.
W.},
Title = {In vitro gene delivery using polyamidoamine dendrimers with
a trimesyl core},
Journal = {Biomacromolecules},
Volume = {6},
Number = {1},
Pages = {341-350},
Year = {2005},
Key = {Article}
}
@article{04518729035,
Author = {Chua, Kian-Ngiap and Lim, Wei-Seng and Zhang, Pengchi and Lu, Hongfang and Wen, Jie and Ramakrishna, Seeram and Leong,
Kam W. and Mao, Hai-Quan},
Title = {Stable immobilization of rat hepatocyte spheroids on
galactosylated nanofiber scaffold},
Journal = {Biomaterials},
Volume = {26},
Number = {15},
Pages = {2537 - 2547},
Year = {2005},
url = {http://dx.doi.org/10.1016/j.biomaterials.2004.07.040},
Keywords = {Cell culture;Copolymers;Biodegradation;Self
assembly;Morphology;Carboxylic acids;},
Abstract = {Primary rat hepatocytes self-assemble into multi-cellular
spheroids and maintain differentiated functions when
cultured on a two-dimensional (2-D) substrate conjugated
with galactose ligand. The aim of this study is to
investigate how a functional nanofiber scaffold with
surface-galactose ligand influences the attachment, spheroid
formation and functional maintenance of rat hepatocytes in
culture, as compared with the functional 2-D substrate.
Highly porous nanofiber scaffolds comprising of fibers with
an average diameter of 760 nm were prepared by
electrospinning of poly(ε-caprolactone-co-ethyl
ethylene phosphate) (PCLEEP), a novel biodegradable
copolymer. Galactose ligand with a density of 66
nmol/cm<sup>2</sup> was achieved on the nanofiber scaffold
via covalent conjugation to a poly(acrylic acid) spacer
UV-grafted onto the fiber surface. Hepatocytes cultured on
the galactosylated PCLEEP nanofiber scaffold exhibited
similar functional profiles in terms of cell attachment,
ammonia metabolism, albumin secretion and cytochrome P450
enzymatic activity as those on the functional 2-D substrate,
although their morphologies are different. Hepatocytes
cultured on galactosylated PCLEEP film formed 50-300 μm
spheroids that easily detached from surface upon agitation,
whereas hepatocytes cultured on galactosylated nanofiber
scaffold formed smaller aggregates of 20-100 μm that
engulfed the functional nanofibers, resulting in an
integrated spheroid-nanofiber construct. © 2004
Elsevier Ltd. All rights reserved.},
Key = {04518729035}
}
@article{070710425378,
Author = {Pan, Wenxiao and Petersen, Erik and Cai, Ning and Ma, Gang and Lee, Jian Run and Feng, Zhiqin and Liao, Kin and Leong,
Kam W.},
Title = {Viscoelastic properties of human mesenchymal stem
cells},
Journal = {Annual International Conference of the IEEE Engineering in
Medicine and Biology - Proceedings},
Volume = {7 S},
Pages = {4854 - 4857},
Address = {Shanghai, China},
Year = {2005},
Keywords = {Antibiotics;Elastic moduli;Mechanical properties;Muscle;Proteins;Viscoelasticity;},
Abstract = {In this study, we investigated the viscoelasticity of
individual bone marrow-derived adult human Mesenchymal Stem
Cells (hMSCs), and the role of specific cytoskeletal
component-F-actin microfilaments on the mechanical
properties of individual hMSCs. The mechanical properties of
hMSCs were determined using the micropipette aspiration
technique coupled with a viscoelastic solid model of the
cell. For the hMSCs under control conditions the
instantaneous Young's modulus E<sub>0</sub> was found to be
886±289(Pa), the equilibrium Young's modulus E<sub>
infinity </sub> 372±125(Pa), and the apparent
viscosity μ, 2714±1626(Pa·S). After exposed
to 2μM of chemical agent-cytochalasin D that disrupt the
F-actin microfilaments, the Young's moduli of hMSCs
decreased by up to 72% and the apparent viscosity increased
by 167%. These findings suggest that microfilaments are
crucial in providing the viscoelastic properties of the
hMSCs, and changes in the structure and properties of them
may influence the mechanical properties of hMSCs
significantly. © 2005 IEEE.},
Key = {070710425378}
}
@article{06279978331,
Author = {Yim, Evelyn K.F. and Leong, Kam W.},
Title = {Significance of synthetic nanostructures in dictating
cellular response},
Journal = {Nanomedicine: Nanotechnology, Biology, and
Medicine},
Volume = {1},
Number = {1},
Pages = {10 - 21},
Year = {2005},
url = {http://dx.doi.org/10.1016/j.nano.2004.11.008},
Keywords = {Medical applications;Substrates;Genes;Adhesion;Biomaterials;Cells;Medicine;},
Abstract = {Cell-substratum interaction is influenced by topographical
in addition to chemical cues. The majority of patterning
studies on cellular response have been conducted on
micropatterned surfaces. Cells clearly respond to the
topography of substrates in the micron range in terms of
adhesion, proliferation, migration, and gene expression.
However, cells in their natural environment also interact
with extracellular matrix components in the nanometer scale.
This review will cover recent studies that show mammalian
cells responding to nanoscale features on a synthetic
surface. An important and exciting direction of research in
nanomedicine would be to gain a better understanding of the
interaction between cells and nanostructures. This will
facilitate the creation of the next generation of
biomaterials with well-defined nanotopography that can
elicit the desired cellular and tissue response. ©
2005.},
Key = {06279978331}
}
@article{Article,
Author = {Chua, K. N. and Lim, W. S. and Zhang, P. C. and Lu, H. F. and Wen, J. and Ramakrishna, S. and Leong, K. W. and Mao, H.
Q.},
Title = {Stable immobilization of rat hepatocyte spheroids on
galactosylated nanofiber scaffold},
Journal = {Biomaterials},
Volume = {26},
Number = {15},
Pages = {2537-2547},
Year = {2005},
Key = {Article}
}
@article{06049665745,
Author = {Lu, Hong-Fang and Lim, Wei Seng and Zhang, Peng-Chi and Chia, Ser Mien and Yu, Hanry and Mao, Hai-Quan and Leong,
Kam W.},
Title = {Galactosylated poly(vinylidene difluoride) hollow fiber
bioreactor for hepatocyte culture},
Journal = {Tissue Engineering},
Volume = {11},
Number = {11-12},
Pages = {1667 - 1677},
Year = {2005},
url = {http://dx.doi.org/10.1089/ten.2005.11.1667},
Keywords = {Bioreactors;Polymers;Adsorption;Proteins;Morphology;Scanning
electron microscopy;Bioassay;Transmission electron
microscopy;},
Abstract = {To overcome the limitations of long-term expression of
highly differentiated hepatocyte functions, we have
developed a novel bioreactor in which hepatocytes are seeded
in a ligand-immobilized hollow fiber cartridge.
Galactosylated Pluronic polymer is immobilized on
poly(vinylidene difluoride) (PVDF) hollow fiber surface
through an adsorption scheme yielding a substrate with
hepatocyte-specific ligand and a hydrophile surface layer,
which can resist nonspecific protein adsorption and
facilitate cell binding to the galactose ligand.
Interestingly, the galactosylated PVDF hollow fiber shows
enhanced serum albumin diffusion across the membrane.
Freshly isolated rat hepatocytes were seeded and cultured in
the extralumenal space of the hollow fiber cartridge for 18
days in a continuously circulated system. Albumin secretion
function of the seeded hepatocytes was monitored by
analyzing circulating medium by enzyme-linked immunosorbent
assay. Urea synthesis and P-450 function (7-ethoxycoumarin
dealkylase activity) were measured periodically by doping
the circulating medium with NH<sub>4</sub>Cl and
7-ethoxycoumarin, respectively. Hepatocytes cultured on
galactosylated PVDF hollow fibers maintained better albumin
secretion and P-450 functions than on unmodified and
serum-coated PVDF hollow fibers when cultured in
serum-containing medium. Morphological examination by
scanning electron microscopy showed that hepatocytes
cultured on galactosylated PVDF hollow fibers developed
significant aggregation, in contrast to those cultured on
unmodified PVDF fibers or on serum-coated PVDF fibers.
Transmission electron microscopy images revealed that tight
junctions and canaliculus-like structures formed in these
aggregates. These results suggest the potential application
of this galactosylated PVDF hollow fiber cartridge for the
design of a bioartificial liver assist device. © Mary
Ann Liebert, Inc.},
Key = {06049665745}
}
@article{05229129061,
Author = {Fang, Ning and Wee, Jin Tan and Leong, Kam W. and Mao,
Hai-Quan and Chan, Vincent},
Title = {pH responsive adhesion of phospholipid vesicle on
poly(acrylic acid) cushion grafted to poly(ethylene
terephthalate) surface},
Journal = {Colloids and Surfaces B: Biointerfaces},
Volume = {42},
Number = {3-4},
Pages = {245 - 252},
Year = {2005},
url = {http://dx.doi.org/10.1016/j.colsurfb.2004.11.002},
Keywords = {pH effects;Acrylics;Phospholipids;Grafting
(chemical);Polyethylene terephthalates;Lipids;Deformation;Polymerization;Ionization;Electrolytes;},
Abstract = {Polymer-supported lipid bilayer is a key enabling technology
for the design and fabrication of novel biomimetic devices.
To date, the physical driving force underlying the formation
of polymer-supported lipid bilayer remains to be determined.
In this study, the interaction between dipalmitoylphosphocholine
(DPPC) vesicle and poly(ethylene terephthalate) [PET]
surface with or without grafted poly(acrylic acid) [PAA]
layer is examined with several biophysical techniques.
First, vesicle deformation analysis shows that the geometry
of adherent vesicle on either plain PET or PAA-grafted PET
surface is best described by a truncated sphere model. At
neutral pH, the degree of deformation and adhesion energy
are unaltered by the grafted polymerization of acrylic acid
on PET surface. Interestingly, the average magnitude of
adhesion energy is increased by 185% and -43% on PAA-grated
PET and plain PET surface, respectively, towards an increase
of pH at room temperature. Our results demonstrate the
possibility of tuning the adhesive interaction between
vesicle and polymer cushion through the control of
polyelectrolyte ionization on the solid support. © 2004
Elsevier B.V. All rights reserved.},
Key = {05229129061}
}
@article{05239140877,
Author = {Liao, I-Chien and Wan, Andrew C.A. and Yim, Evelyn K.F. and Leong, Kam W.},
Title = {Controlled release from fibers of polyelectrolyte
complexes},
Journal = {Journal of Controlled Release},
Volume = {104},
Number = {2},
Pages = {347 - 358},
Year = {2005},
url = {http://dx.doi.org/10.1016/j.jconrel.2005.02.013},
Keywords = {Fibers;Polyelectrolytes;Complexation;Proteins;Interfaces
(materials);},
Abstract = {Controlled release systems for delicate compounds, such as
proteins, often suffer the drawbacks of decreased
bioactivity and low encapsulation efficiency. This study
introduces the concept of producing drug-loaded fibers from
interfacial polyelectrolyte complexation. Chitosan-alginate
fibers were produced by pulling from the interface between
two polyelectrolyte solutions at room temperature. Depending
on the component properties, the release time of
encapsulated components from these fibers can range from
hours to weeks. Dexamethasone was completely released within
2 h, whereas charged compounds such as BSA, PDGF-bb, and
avidin showed sustained release for 3 weeks. The fibers were
able to release PDGF-bb in a steady fashion for over 3 weeks
without an initial burst. Furthermore, the bioactivity of
PDGF-bb was retained over this period. Release kinetics
could be controlled by the inclusion of heparin, which
contains specific binding sites for various growth factors.
By varying the alginate/heparin ratios in the anionic
polyelectrolyte solution, the release of PDGF-bb could be
significantly altered. In this study, interfacial
polyelectrolyte complexation has been demonstrated to be a
promising technique for producing drug-loaded fibers with
high encapsulation efficiency, sustained release kinetics,
and capacity to retain the bioactivity of the encapsulants.
© 2005 Elsevier B.V. All rights reserved.},
Key = {05239140877}
}
@article{05419410110,
Author = {Li, Jun and Ni, Xiping and Li, Xu and Tan, Ngee Koon and Lim, Chwee Teck and Ramakrishna, Seeram and Leong, Kam
W.},
Title = {Micellization phenomena of biodegradable amphiphilic
triblock copolymers consisting of poly(β-hydroxyalkanoic
acid) and poly(ethylene oxide)},
Journal = {Langmuir},
Volume = {21},
Number = {19},
Pages = {8681 - 8685},
Year = {2005},
url = {http://dx.doi.org/10.1021/la0515266},
Keywords = {Biodegradation;Copolymers;Carboxylic acids;Polyethylene
oxides;Transmission electron microscopy;},
Abstract = {This paper reports the studies on micelle formation of new
biodegradable amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene
oxide) (PEO-PHB-PEO) triblock copolymer with various PHB and
PEO block lengths in aqueous solution. Transmission electron
microscopy showed that the micelles took an approximately
spherical shape with the surrounding diffuse outer shell
formed by hydrophilic PEO blocks. The size distribution of
the micelles formed by one triblock copolymer was
demonstrated by dynamic light scattering technique. The
critical micellization phenomena of the copolymers were
extensively studied using the pyrene fluorescence dye
absorption technique, and the (0,0) band changes of pyrene
excitation spectra were used as a probe for the studies. For
the copolymers studied in this report, the critical micelle
concentrations ranged from 1.3 × 10<sup>-5</sup> to
1.1 × 10 <sup>-3</sup> g/mL. For the same PEO block
length of 5000, the critical micelle concentrations
decreased with an increase in PHB block length, and the
change was more significant in the short PHB range. It was
found that the micelle formation of the biodegradable
amphiphilic triblock copolymers consisting of
poly(β-hydroxyalkanoic acid) and PEO was relatively
temperature- insensitive, which is quite different from
their counterparts consisting of poly(α-hydroxyalkanoic
acid) and PEO. © 2005 American Chemical
Society.},
Key = {05419410110}
}
@article{05108867730,
Author = {Zhang, Peng-Chi and Wang, Jun and Leong, Kam W. and Mao,
Hai-Quan},
Title = {Ternary complexes comprising polyphosphoramidate gene
carriers with different types of charge groups improve
transfection efficiency},
Journal = {Biomacromolecules},
Volume = {6},
Number = {1},
Pages = {54 - 60},
Year = {2005},
url = {http://dx.doi.org/10.1021/bm040010i},
Keywords = {Genes;Synthesis (chemical);Biodegradation;DNA;Amino
acids;Titration;},
Abstract = {To understand the influence of charge groups on transfection
mediated by polymer complexes, we have synthesized a series
of biodegradable and cationic polyphosphoramidates (PPAs)
with an identical backbone but different side chains. Our
previous study showed that PPA with a spermidine side chain
(PPA-SP) showed high transfection efficiency in culture,
whereas PPAs with secondary, tertiary, and quaternary amino
groups were significantly less efficient. To investigate
whether the coexistence of 1° amino charge groups with
3° and 2° amino charge groups in the DNA/polymer
complexes would enhance their transfection efficiency, we
evaluated a ternary complex system containing DNA and PPAs
with 1° amino groups (PPA-SP) and 3° amino groups
(PPA-DMA) and a quaternary complex system containing DNA and
PPAs with 1° and 2° and 3° amino groups
(PPA-EA/PPA-MEA/PPA-DMA), respectively. Ternary complexes
mediated 20 and 160 times higher transfection efficiency in
COS-7 cells than complexes of DNA with PPA-SP or PPA-DMA
alone, respectively. Similarly, quaternary complexes
exhibited 8-fold higher transfection efficiency than
PPA-EA/DNA complexes. The mechanism of enhancement in
transfection efficiency by the mixture carriers appears to
be unrelated to the particle size, zeta potential, or DNA
uptake. The titration characterization and the transfection
experiments using a proton pump inhibitor suggest that the
enhancement effect is unlikely due to the slightly improved
buffering capacity of the mixture over PPA-SP. This approach
represents a simple strategy of developing polymeric gene
carriers and understanding the mechanisms of
polymer-mediated gene transfer. © 2005 American
Chemical Society.},
Key = {05108867730}
}
@article{Article,
Author = {Chia, S. M. and Lin, P. C. and Quek, C. H. and Yin, C. and Mao, H. Q. and Leong, K. W. and Xu, X. and Goh, C. H. and Ng, M. L. and Yu, H.},
Title = {Engineering microenvironment for expansion of sensitive
anchorage-dependent mammalian cells},
Journal = {Journal of Biotechnology},
Volume = {118},
Number = {4},
Pages = {434-447},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Li, J. and Ni, X. P. and Li, X. and Tan, N. K. and Lim, C.
T. and Ramakrishna, S. and Leong, K. W.},
Title = {Micellization phenomena of biodegradable amphiphilic
triblock copolymers consisting of poly(beta-hydroxyalkanoic
acid) and poly(ethylene oxide)},
Journal = {Langmuir},
Volume = {21},
Number = {19},
Pages = {8681-8685},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Tan, W. J. and Teo, G. P. and Liao, K. and Leong, K. W. and Mao, H. Q. and Chan, V.},
Title = {Adhesion contact dynamics of primary hepatocytes on
poly(ethylene terephthalate) surface},
Journal = {Biomaterials},
Volume = {26},
Number = {8},
Pages = {891-898},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Kim, M. S. and Hwang, N. S. and Lee, J. and Kim, T. K. and Leong, K. and Shamblott, M. J. and Gearhart, J. and Elisseeff, J.},
Title = {Musculoskeletal differentiation of cells derived from human
embryonic germ cells},
Journal = {Stem Cells},
Volume = {23},
Number = {1},
Pages = {113-123},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Liu, Y. and Wu, D. C. and Zhang, W. D. and Jiang, X. and He,
C. B. and Chung, T. S. and Goh, S. H. and Leong, K.
W.},
Title = {Polyethylenimine-grafted multiwalled carbon nanotubes for
secure noncovalent immobilization and efficient delivery of
DNA},
Journal = {Angewandte Chemie-International Edition},
Volume = {44},
Number = {30},
Pages = {4782-4785},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Zhang, P. C. and Wang, J. and Leong, K. W. and Mao, H.
Q.},
Title = {Ternary complexes comprising polyphosphoramidate gene
carriers with different types of charge groups improve
transfection efficiency},
Journal = {Biomacromolecules},
Volume = {6},
Number = {1},
Pages = {54-60},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Mao, H. Q. and Shipanova-Kadiyala, I. and Zhao, Z. and Dang,
W. B. and Brown, A. and Leong, K. W.},
Title = {Biodegradable poly(terephthalate-co-phosphate)s: synthesis,
characterization and drug-release properties},
Journal = {Journal of Biomaterials Science-Polymer Edition},
Volume = {16},
Number = {2},
Pages = {135-161},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Chen, H. H. and Le Visage and C. and Qiu, B. S. and Du, X. Y. and Ouwerkerk, R. and Leong, K. W. and Yang, X.
M.},
Title = {MR imaging of biodegradable polymeric microparticles: A
potential method of monitoring local drug
delivery},
Journal = {Magnetic Resonance in Medicine},
Volume = {53},
Number = {3},
Pages = {614-620},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Wu, D. C. and Liu, Y. and Jiang, X. and Chen, L. and He, C.
B. and Goh, S. H. and Leong, K. W.},
Title = {Evaluation of hyperbranched poly(amino ester)s of amine
constitutions similar to polyethylenimine for DNA
delivery},
Journal = {Biomacromolecules},
Volume = {6},
Number = {6},
Pages = {3166-3173},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Salem, A. K. and Hung, C. F. and Kim, T. W. and Wu, T. C. and Searson, P. C. and Leong, K. W.},
Title = {Multi-component nanorods for vaccination
applications},
Journal = {Nanotechnology},
Volume = {16},
Number = {4},
Pages = {484-487},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Yim, E. K. F. and Reano, R. M. and Pang, S. W. and Yee, A.
F. and Chen, C. S. and Leong, K. W.},
Title = {Nanopattern-induced changes in morphology and motility of
smooth muscle cells},
Journal = {Biomaterials},
Volume = {26},
Number = {26},
Pages = {5405-5413},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Lu, H. F. and Chua, K. N. and Zhang, P. C. and Lim, W. S. and Ramakrishna, S. and Leong, K. W. and Mao, H.
Q.},
Title = {Three-dimensional co-culture of rat hepatocyte spheroids and
NIH/3T3 fibroblasts enhances hepatocyte functional
maintenance},
Journal = {Acta Biomaterialia},
Volume = {1},
Number = {4},
Pages = {399-410},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Chew, S. Y. and Wen, J. and Yim, E. K. F. and Leong, K.
W.},
Title = {Sustained release of proteins from electrospun biodegradable
fibers},
Journal = {Biomacromolecules},
Volume = {6},
Number = {4},
Pages = {2017-2024},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Fang, N. and Tan, W. J. and Leong, K. W. and Mao, H. Q. and Chan, V.},
Title = {pH responsive adhesion of phospholipid vesicle on
poly(acrylic acid) cushion grafted to poly(ethylene
terephthalate) surface},
Journal = {Colloids and Surfaces B-Biointerfaces},
Volume = {42},
Number = {3-4},
Pages = {245-252},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Yim, E. K. F. and Leong, K. W.},
Title = {Proliferation and differentiation of human embryonic germ
cell derivatives in bioactive polymeric fibrous
scaffold},
Journal = {Journal of Biomaterials Science-Polymer Edition},
Volume = {16},
Number = {10},
Pages = {1193-1217},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Kuang, M. and Liu, S. Q. and Saijo, K. and Uchimura, E. and Huang, L. and Leong, K. W. and Lu, M. D. and Huang, J. F. and Ohno, T.},
Title = {Microwave tumour coagulation plus in situ treatment with
cytokine-microparticles: Induction of potent anti-residual
tumour immunity},
Journal = {International Journal of Hyperthermia},
Volume = {21},
Number = {3},
Pages = {247-257},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Zhang, X. Q. and Wang, X. L. and Zhang, P. C. and Liu, Z. L. and Zhuo, R. X. and Mao, H. Q. and Leong, K.
W.},
Title = {Galactosylated ternary DNA/polyphosphoramidate nanoparticles
mediate high gene transfection efficiency in
hepatocytes},
Journal = {Journal of Controlled Release},
Volume = {102},
Number = {3},
Pages = {749-763},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Mao, H. Q. and Leong, K. W.},
Title = {Design of polyphosphoester-DNA nanoparticles for non-viral
gene delivery},
Journal = {Adv Genet},
Volume = {53},
Pages = {275-306},
Year = {2005},
Keywords = {Biological Transport/physiology DNA/genetics/*metabolism
Gene Therapy/*methods *Gene Transfer Techniques Genetic
Vectors/genetics/*metabolism Imidazoles/chemistry/metabolism
*Nanostructures Phosphoric Acid Esters/chemistry/*metabolism
Plasmids/genetics/physiology Polymers/chemistry/*metabolism},
Abstract = {Development of safe and effective non-viral gene carriers is
still critical to the ultimate success of gene therapy. This
review highlights our attempt to design the gene carriers in
a systematic manner. We have synthesized a series of
polymers with a phosphoester backbone containing different
charge groups in the sidechain connected to the backbone
through a phosphate (P-O) or a phosphoramide (P-N) bond.
These gene carriers have different charge groups, sidechain
lengths, and branching structures, but they are structurally
related to allow a systematic investigation of the
structure-property relationship, including DNA binding
capacity, cytotoxicity, DNA protection, biodegradability,
DNA release kinetics, and transfection efficiency.},
Key = {Article}
}
@article{Article,
Author = {Liao, I. C. and Wan, A. C. A. and Yim, E. K. F. and Leong,
K. W.},
Title = {Controlled release from fibers of polyelectrolyte
complexes},
Journal = {Journal of Controlled Release},
Volume = {104},
Number = {2},
Pages = {347-358},
Year = {2005},
Key = {Article}
}
@article{Article,
Author = {Hu, W. and Yim, E. K. F. and Reano, R. M. and Leong, K. W. and Pang, S. W.},
Title = {Effects of nanoimprinted patterns in tissue-culture
polystyrene on cell behavior},
Journal = {Journal of Vacuum Science & Technology B},
Volume = {23},
Number = {6},
Pages = {2984-2989},
Year = {2005},
Key = {Article}
}
@article{8420448,
Author = {Chen, H.H. and Le Visage and C. and Bensheng Qiu and Xiangying
Du and Ouwerkerk, R. and Leong, K.W. and Xiaoming
Yang},
Title = {MR imaging of biodegradable polymeric microparticles: a
potential method of monitoring local drug
delivery},
Journal = {Magn. Reson. Med. (USA)},
Volume = {53},
Number = {3},
Pages = {614 - 20},
Year = {2005},
url = {http://dx.doi.org/10.1002/mrm.20395},
Keywords = {biological organs;biomedical MRI;drug delivery
systems;polymers;},
Abstract = {Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) was
encapsulated into biodegradable, bioadhesive polymeric
microparticles to enable noninvasive monitoring of their
local intravesical delivery with MRI. The microparticles
were characterized by contrast agent encapsulation and
release kinetics, T<sub>1</sub> relaxation rates, and
contrast enhancement in vivo. The level of Gd-DTPA loading
into microparticles was 14.3±0.6 μg/mg polymer.
The measured T<sub>1</sub> relaxation rates of the
microparticles showed a direct dependence on Gd-DPTA
content. Both 1.5T and 4.7T MR scanners were used to image
murine bladders instilled intravesically with Gd-DPTA-loaded
particles in vivo. MR images showed ring-shaped regions of
enhancement inscribing the bladder wall, which were
attributed to the microparticles that were preferentially
adherent to the mucosa lining the urothelium. The images of
controls exhibited no such enhancement. The normalized
signal intensities measured from postinstillation images
were significantly greater (P< 0.05) than those in the
preinstillation images. Contrast enhancement was observed
for at least 5 days after the initial instillation, although
the enhancement decreased due to microparticle degradation
or mucosa renewal. The localized distribution of
biodegradable, bioadhesive microparticles encapsulating
Gd-DTPA was successfully visualized with MRI in vivo,
allowing particle-mediated delivery to be temporally and
spatially monitored noninvasively},
Key = {8420448}
}
@article{Article,
Author = {Li, Y. and Wang, J. and Lee, C. G. L. and Wang, C. Y. and Gao, S. J. and Tang, G. P. and Ma, Y. X. and Yu, H. and Mao,
H. Q. and Leong, K. W. and Wang, S.},
Title = {CNS gene transfer mediated by a novel controlled release
system based on DNA complexes of degradable polycation
PPE-EA: a comparison with polyethylenimine/DNA
complexes},
Journal = {Gene Therapy},
Volume = {11},
Number = {1},
Pages = {109-114},
Year = {2004},
Key = {Article}
}
@article{04408390979,
Author = {Shin-Ya, Yoshitsune and Tsurushima, Hideo and Tsurumi, Taro and Kajiuchi, Toshio and Leong, Kam W.},
Title = {Polyelectrolyte complex films derived from
polyethyleneoxide-maleic acid copolymer and chitosan:
Preparation and characterization},
Journal = {Macromolecular Bioscience},
Volume = {4},
Number = {5},
Pages = {526 - 531},
Year = {2004},
url = {http://dx.doi.org/10.1002/mabi.200300110},
Keywords = {Thin films;Polyethylene oxides;Copolymers;Solvents;Evaporation;Infrared
radiation;Surfaces;pH effects;Biomedical equipment;Drug
dosage;},
Abstract = {Polyelectrolyte complex films were prepared with
polyethyleneoxide-maleic acid copolymer and chitosan using a
casting/solvent evaporation method. The films were examined
in terms of their IR spectra, surface and cross-section
morphologies, cytotoxicity, and swelling behavior at
different pH levels. To assess the potential of these films
as a biomedical device, the profiles of the release of model
drug from the CS/PEOMA films were examined at pH 4.8. The
surface morphology of the films was quite smooth and
uniform, and the cross-sectional morphology was dense and
homogeneous. The swelling behaviors of CS/PEOMA films were
found to depend on the pH of the solution as well as on the
CS/PEOMA composition. Drug release from different CS/PEOMA
films at pH 4.8 was found to be dependent on film
composition. The results showed the potential applicability
of CS/PEOMA film as a drug delivery vehicle.},
Key = {04408390979}
}
@article{8297735,
Author = {Kiang, T. and Bright, C. and Cheung, C.Y. and Stayton, P.S. and Hoffman, A.S. and Leong, K.W.},
Title = {Formulation of chitosan-DNA nanoparticles with poly(propyl
acrylic acid) enhances gene expression},
Journal = {J. Biomater. Sci., Polym. Ed. (Netherlands)},
Volume = {15},
Number = {11},
Pages = {1405 - 21},
Year = {2004},
url = {http://dx.doi.org/10.1163/1568562042368112},
Keywords = {biochemistry;biomedical materials;biomembranes;DNA;drugs;genetics;lipid
bilayers;molecular biophysics;nanoparticles;patient
treatment;polymers;},
Abstract = {Poly(propyl acrylic acid) (PPAA) is a polymer specifically
designed to disrupt lipid bilayer membranes within a sharply
defined pH range. The pH sensitivity can be used to enhance
the release of endocytosed drugs into the cytoplasmic
compartment of the cell. By incorporating this polymer in a
polymeric gene carrier, chitosan, the release of plasmid DNA
from the endosomal compartment was enhanced. In vitro
transfection studies confirmed that the incorporation of
PPAA into the chitosan-DNA nanoparticles enhanced gene
expression in both HEK293 and HeLa cells compared to
chitosan nanoparticles alone. The dose and time at which
PPAA was incorporated during the complex formation affected
the release of DNA and transfection efficiency. The optimal
dose of PPAA incorporated into the chitosan nanoparticles
was determined to be 10 μg, corresponding to a PPAA/DNA
weight ratio of 1:1. At this dose, the ternary complexes are
approx. 400 nm in size with a net negative surface charge of
-17.4 mV. Intracellular trafficking studies confirmed the
association of PPAA, DNA and chitosan at 24 h
post-transfection and the subsequent release of DNA and PPAA
from the chitosan at 48 h. The diffuse appearance of the
majority of the DNA and the PPAA at later time points
suggests that the PPAA triggered membrane disruption
resulting in the release of DNA from the endosomal
compartment. Finally, the lack of colocalization between
PPAA and Lysotracker indicated that the PPAA-loaded
nanoparticles were not trafficked through a lysosomal
pathway. This study suggests the promising strategy of
including PPAA in the formulation of polymer-DNA complexes
for nonviral gene delivery},
Key = {8297735}
}
@article{04508714054,
Author = {Le Visage and Catherine and Dunham, Brian and Flint, Paul and Leong, Kam W.},
Title = {Coculture of mesenchymal stem cells and respiratory
epithelial cells to engineer a human composite respiratory
mucosa},
Journal = {Tissue Engineering},
Volume = {10},
Number = {9-10},
Pages = {1426 - 1435},
Year = {2004},
url = {http://dx.doi.org/10.1089/1076327042500247},
Keywords = {Respiratory system;Cells;Cytology;Bone;Biological
membranes;Histology;Mathematical models;},
Abstract = {In this study, we describe a novel in vitro reconstitution
system for tracheal epithelium that could be useful for
investigating the cellular and molecular interaction of
epithelial and mesenchymal cells. In this system, a
Transwell insert was used as a basement membrane on which
adult bone marrow mesenchymal stem cells (MSCs) were
cultured on the lower side whereas normal human bronchial
epithelial (NHBE) cells were cultured on the opposite upper
side. Under air-liquid interface conditions, the epithelial
cells maintained their capacity to progressively
differentiate and form a functional epithelium, leading to
the differentiation of mucin-producing cells between days 14
and 21. Analysis of apical secretions showed that mucin
production increased over time, with peak secretion on day
21 for NHBE cells alone, whereas mucin secretion by NHBE
cells cocultured with MSCs remained constant between days 18
and day 25. This in vitro model of respiratory epithelium,
which exhibited morphologic, histologic, and functional
features of a tracheal mucosa, could help to understand
interactions between mesenchymal and epithelial cells and
mechanisms involved in mucus production, inflammation, and
airway repair. It might also play an important role in the
design of an composite prosthesis for tracheal
replacement.},
Key = {04508714054}
}
@article{Article,
Author = {Kuang, M. and Peng, B. G. and Lu, M. D. and Liang, L. J. and Huang, J. F. and He, Q. and Hua, Y. P. and Totsuka, S. and Liu, S. Q. and Leong, K. W. and Ohno, T.},
Title = {Phase II randomized trial of autologous formalin-fixed tumor
vaccine for postsurgical recurrence of hepatocellular
carcinoma},
Journal = {Clinical Cancer Research},
Volume = {10},
Number = {5},
Pages = {1574-1579},
Year = {2004},
Key = {Article}
}
@article{05098858328,
Author = {Wan, A.C.A. and Yim, E.K.F. and Liao, I.-C. and Chai, C. and Leong, K.W.},
Title = {The assembly of "biostructural units" as a new strategy for
tissue engineering},
Journal = {Transactions - 7th World Biomaterials Congress},
Pages = {1543 -},
Address = {Sydney, Australia},
Year = {2004},
Keywords = {Tissue;Cells;Polyelectrolytes;Complexation;Fluorescence;Immunology;Microscopic
examination;},
Abstract = {The concept of 'biostructural units' for application in
tissue engineering was presented. The process of interfacial
polyelectrolyte complexation (IPC) was employed. By means of
processes like hydroentanglement and needle-punching,
scaffolds were created from both wet and dry fibers for
tissue engineering. It was found that the formation of
scaffolds and constructs via the assembly of biostructural
units can provide for better spatial definition.},
Key = {05098858328}
}
@article{05098857694,
Author = {Chai, C. and Feng, Q. and Jiang, X.S. and Leong, K.W. and Mao, H.Q.},
Title = {Expansion of CD34+ cells on polymeric scaffolds
surface-immobilized with hematopoietic growth
factors},
Journal = {Transactions - 7th World Biomaterials Congress},
Pages = {897 -},
Address = {Sydney, Australia},
Year = {2004},
Keywords = {Biomaterials;Polyethylene terephthalates;Growth
kinetics;Cell immobilization;Cell membranes;Solubility;Bone;Cytology;Oxidation;},
Abstract = {The expansion of CD34+ hematopoietic stem cells (HSC) on
two-dimensional (2D) and three-dimensional (3D) polymeric
scaffolds, surface-immobilized with hematopoietic growth
factors (HGF), was investigated. The polymeric scaffolds
were prepared by functionalizing polyethylene terephthalate
(PET) film disks and non-woven disks with carboxyl (COOH)
groups by oxidation with potassium permanganate. Stem cell
factor (SCF) and IL-6 HGFs were covalently immobilized
individually or concomitantly into PET-COOH via amide bond
formation. It was observed that immobilized IL-6 on 2D PET
surface induced a dramatic expansion of CD34+ cells,
contributed largely by expansion of progenitor cells with
multi-lineage potential.},
Key = {05098857694}
}
@article{04398379543,
Author = {Wan, Andrew C.A. and Liao, I.-Chien and Yim, Evelyn K.F. and Leong, Kam W.},
Title = {Mechanism of fiber formation by interfacial polyelectrolyte
complexation},
Journal = {Macromolecules},
Volume = {37},
Number = {18},
Pages = {7019 - 7025},
Year = {2004},
url = {http://dx.doi.org/10.1021/ma0498868},
Keywords = {Polyelectrolytes;Complexation;Scattering;Coalescence;Turbidity;Antireflection
coatings;Ionization;Acetic acid;Dialysis
membranes;},
Abstract = {A four-step mechanism is hypothesized for the process of
fiber formation by interfacial polyelectrolyte complexation:
(1) formation of a polyionic complex film at the interface
that acts as a viscous barrier to free mixing; (2)
scattering of this complex by a drawing motion, creating
submicron "nuclear fibers"; (3) growth of "nuclear fibers",
with an accompanying decrease in the viscosity of the
surrounding polyelectrolyte matrix; (4) coalescence of
"nuclear fibers", resulting in a thicker primary fiber and
gel droplets at regular intervals along its axis. Presented
evidence include light and confocal microscopy of the fiber
structure, detailed observation of the fiber drawing
process, turbidity experiments to measure the stability of
the interface, effect of polyelectrolyte solution
concentrations and contact area at the interface on fiber
dimensions, and identification of two critical draw rates
that can be related to the proposed fiber-forming
mechanism.},
Key = {04398379543}
}
@article{Article,
Author = {Li, X. and Li, J. and Leong, K. W.},
Title = {Role of intermolecular interaction between hydrophobic
blocks in block-selected inclusion complexation of
amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene
oxide) triblock copolymers with cyclodextrins},
Journal = {Polymer},
Volume = {45},
Number = {20},
Pages = {6845-6851},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Faranesh, A. Z. and Nastley, M. T. and de la Cruz, C. P. and Haller, M. F. and Laquerriere, P. and Leong, K. W. and McVeigh, E. R.},
Title = {In vitro release of vascular endothelial growth factor from
gadolinium-doped biodegradable microspheres},
Journal = {Magnetic Resonance in Medicine},
Volume = {51},
Number = {6},
Pages = {1265-1271},
Year = {2004},
Key = {Article}
}
@article{05098858532,
Author = {Chua, K.N. and Lim, W.S. and Lu, H.F. and Chai, C. and Zhang, P.C. and Wen, J. and Ramakrishna, S. and Leong, K.W. and Mao, H.Q.},
Title = {Immobilized hepatocyte spheroids on galactose
ligand-conjugated nanofiber scaffold},
Journal = {Transactions - 7th World Biomaterials Congress},
Pages = {1753 -},
Address = {Sydney, Australia},
Year = {2004},
Keywords = {Enzyme inhibition;Fibers;Nanostructured materials;Monolayers;Scaffolds;Polyethylene
terephthalates;Thin films;Substrates;Synthesis
(chemical);Polymerization;Morphology;},
Abstract = {The effect of nanofiber scaffold on hepatocyte attachment,
migration, spheroid formation and maintenance if the
differentiated functions was analyzed. A hepatocyte specific
nanofiber scaffold was synthesized by conjugating
1-O-(6'-aminohexyl)-D-galactopyranoside (AHG) galactose
ligands to the poly(acrylic acid) grafted polycaprolactone
(PCL)-co- ethylethylene phosphate (EEP) nanofiber mesh. It
was found that hepatocytes cultured on galactosylated
PCL-co-EEP nanofiber scaffolds and thin film substrates
exhibited similarly high hepatocyte attachment (~80-90%).
The results show that the nanofiber scaffolds exhibits
unique properties of promoting hepatocyte aggregates within
the spaces and around the fiber.},
Key = {05098858532}
}
@article{05098858590,
Author = {Lim, W.S. and Chua, K.N. and Wang, X.L. and Zhang, P.C. and Lu, H.F. and Leong, K.W. and Mao, H.Q.},
Title = {Transfection of rat primary hepatocytes using a novel
polyphosphoramidate gene carrier},
Journal = {Transactions - 7th World Biomaterials Congress},
Pages = {1813 -},
Address = {Sydney, Australia},
Year = {2004},
Keywords = {Cells;Proteins;Monolayers;Collagen;Tissue;Polystyrenes;Synthesis
(chemical);DNA;High performance liquid chromatography;Polyethylene
terephthalates;},
Abstract = {The transfectability of the hepatocyte spheroids in
comparison with hepatocyte monolayer was investigated using
a novel non-viral polycationic gene carrier,
polyphosphoramidate containing diethylamine side chains
(PPA-DEA). The optimal window for transfection after cell
seeding and culture was also determined. Using ELISA and
HPLC techniques, hepatocyte-specific functions such as
albumin secretion and P450 activity were measured. PPA-DEA
was found to be a viable non-viral gene carrier since it
produces reasonable transgene expression and has no adverse
effects on the hapatocyte-specific functions.},
Key = {05098858590}
}
@article{04198153599,
Author = {Bini, T.B. and Gao, Shujun and Xu, Xiaoyun and Wang, Shu and Ramakrishna, S. and Leong, Kam W.},
Title = {Peripheral nerve regeneration by microbraided
poly(L-lactide-co-glycolide) biodegradable polymer
fibers},
Journal = {Journal of Biomedical Materials Research - Part
A},
Volume = {68},
Number = {2},
Pages = {286 - 295},
Year = {2004},
url = {http://dx.doi.org/10.1002/jbm.a.20050},
Keywords = {Neurology;Biodegradation;Polymers;Hydrolysis;Morphology;Biocompatibility;Scanning
electron microscopy;Implants (surgical);Swelling;},
Abstract = {Tiny tubes with fiber architecture were developed by a novel
method of fabrication upon introducing some modification to
the microbraiding technique, to function as nerve guide
conduit and the feasibility of in vivo nerve regeneration
was investigated through several of these conduits.
Poly(L-lactide-co-glycolide) (10:90) polymer fibers being
biocompatible and biodegradable were used for the
fabrication of the conduits. The microbraided nerve guide
conduits (MNGCs) were characterized using scanning electron
microscopy to study the surface morphology and fiber
arrangement. Degradation tests were performed and the
micrographs of the conduit showed that the degradation of
the conduit is by fiber breakage indicating bulk hydrolysis
of the polymer. Biological performances of the conduits were
examined in the rat sciatic nerve model with a 12-mm gap.
After implantation of the MNGC to the right sciatic nerve of
the rat, there was no inflammatory response. One week after
implantation, a thin tissue capsule was formed on the outer
surface of the conduit, indicating good biological response
of the conduit. Fibrin matrix cable formation was seen
inside the MNGC after 1 week implantation. One month after
implantation, 9 of 10 rats showed successful nerve
regeneration. None of the implanted tubes showed tube
breakage. The MNGCs were flexible, permeable, and showed no
swelling apart from its other advantages. Thus, these new
poly(L-lactide-co-glycolide) microbraided conduits can be
effective aids for nerve regeneration and repair and may
lead to clinical applications. © 2003 Wiley
Periodicals, Inc.},
Key = {04198153599}
}
@article{04148101161,
Author = {Chan, Vincent and Liu, Kuo-Kang and Le Visage and Catherine and Ju, Bin-Feng and Leong, Kam W.},
Title = {Bioadhesive characterization of poly(methylidene malonate
2.12) microparticle on model extracellular
matrix},
Journal = {Biomaterials},
Volume = {25},
Number = {18},
Pages = {4327 - 4332},
Year = {2004},
url = {http://dx.doi.org/10.1016/j.biomaterials.2003.11.021},
Keywords = {Tissue;Drug products;Collagen;pH effects;Adhesion;Deformation;Elastic
moduli;Characterization;},
Abstract = {The efficacy of a drug delivery system is predicated on its
retention in the target tissue. Microparticle is one of the
most popular and effective drug delivery configurations.
Recently, it has been shown that the interaction between
drug-loaded microparticles and tissues is related to the
effectiveness of paclitaxel delivery to the bladder wall of
mice for treating superficial bladder cancer. In this study,
the adhesive interaction between poly(methylidene malonate
2.12) or PMM 2.1.2 microparticles and collagen, which serves
as the model extracellular matrix for bladder wall, was
probed with confocal reflectance interference contrast
microscopy (C-RICM), single-particle compressive force
measurement and contact mechanics theory. Young's modulus of
single PMM 2.1.2 microparticle was determined as
1.56±0.25×10 <sup>4</sup>N/m<sup>2</sup>. For
plain PMM 2.1.2 microparticle in water (pH 5.5), the degree
of deformation (a/R) on collagen coated substrate decreased
from 0.77 to 0.26 against the increase of mid-plane diameter
from 2 to 18μm. The adhesion energy of PMM 2.1.2
microparticle was determined from Maguis-JKR theory and
remained at around 1.5mJ/m<sup>2</sup> against the increase
of particle diameter. At pH 4, the average degree of
particle deformation and adhesion energy was increased by
11% and 32%, respectively, in comparison with that at pH
5.5. The loading of paclitaxel in PMM 2.1.2 microspheres
enhanced the deformation and adhesion of microspheres at pH
5.5. It is hypothesized that the electrostatic repulsion
between paclitaxel and collagen at pH 4 reduces the adhesion
energy of PMM 2.1.2-paclitaxel microsphere. This study may
offer insight for design of future microparticulate delivery
systems by providing the experimental and theoretical tools
to study the bioadhesive interaction between drug-loaded
microparticles and model extracellular matrices. © 2003
Elsevier Ltd. All rights reserved.},
Key = {04148101161}
}
@article{05098856981,
Author = {Yim, E.K.F. and Wan, A. and Liao, I. and Le Visage and C. and Leong, K.W.},
Title = {Osteogenic and chondrogenic differentiation of human
mesenchymal stem cells incorporated into polyelectrolyte
fibrous scaffold},
Journal = {Transactions - 7th World Biomaterials Congress},
Pages = {165 -},
Address = {Sydney, Australia},
Year = {2004},
Keywords = {Scaffolds;Polyelectrolytes;Substrates;Proteins;Drug
products;Fibers;Adhesion;Chitin;Molecular
weight;Bioassay;RNA;Microscopic examination;Histology;},
Abstract = {Scaffold is an important component in tissue engineering
application by providing substrate and support for tissue
development. We have recently developed a novel
biodegradable polyelectrolyte fibrous bioconstruct system
where protein, growth factors, drugs and cells can be
incorporated into the fiber, while growth factors and
adhesion molecules can be immobilized on the fiber surface.
Such a bioconstruct system would allow development of tissue
with multiple cell types and/or structures. Human
mesenchymal stem cells (hMSC) have the potential to
differentiate into lineages of mesenchymal tissue (1). To
explore the potential of this bioconstruct system, hMSC were
incorporated into fibers composed of alginate and chitin.
The proliferation, osteogenic and chondrogenic
differentiation of the entrapped hMSC were examined in this
study.},
Key = {05098856981}
}
@article{04258224801,
Author = {Sun, Daniel D.N. and Leong, Kam W.},
Title = {A nonlinear hyperelastic mixture theory model for
anisotropy, transport, and swelling of annulus
fibrosus},
Journal = {Annals of Biomedical Engineering},
Volume = {32},
Number = {1},
Pages = {92 - 102},
Year = {2004},
url = {http://dx.doi.org/10.1023/B:ABME.0000007794.87408.1e},
Keywords = {Anisotropy;Joints (anatomy);Mixtures;Deformation;Compression
testing;Swelling;Composition;},
Abstract = {A precise knowledge of the local mechanical and chemical
environment around the nerve endings and disc cells in the
annulus fibrosus will shed insight on understanding the
mechanism of low-back pain and disc degeneration. It would
also present an effective tool for the studies of the
intervertebral disc structure-function relationship and
provide guidance to disc tissue engineering. Experimental
difficulties preclude the direct and simultaneous
measurement of many of the important physical quantities,
such as annulus pressurization, nutrient and electrolyte
transport, and mechanical and swelling deformation.
Considering that many of these quantities are coupled and
that the annulus is highly anisotropic, interpretation of
the results would be extremely challenging without an
appropriate theoretical framework. In this study, we develop
a nonlinear hyperelastic fiber-reinforced continuum mixture
theory model for the annulus fibrosus. Special attention is
given to the anisotropic nature of the annulus. On the basis
of the lamella structure of annulus, and derived from a
Helmholtz energy function, a locally transversely isotropic
stress-strain relation is adopted for explicit
representation of the collagen fiber orientations in general
finite deformation situation. The exponential form of the
Helmholtz energy function naturally reduces to the
infinitesimal deformation form, and the equivalence between
the current model coefficients and engineering elastic
constants is established under the infinitesimal
deformation. This model is able to describe the anisotropic
finite and infinitesimal deformation, tension-compression
nonlinearity, osmotic swelling, pressurization, electrical
potential and current, and water and ion transports as well
as the electroneutral nutrient (or growth factor) transport
within the annulus.},
Key = {04258224801}
}
@article{05098857471,
Author = {Li, X. and Ni, X.P. and Zhou, Z.H. and Leong, K.W. and Li,
J.},
Title = {Injectable supramolecular hydrogels based on poly(ethylene
oxide)-b-poly[(R)-3-hydroxybutyrate]-b-poly(ethylene oxide)
triblock copolymers and α-cyclodextrin},
Journal = {Transactions - 7th World Biomaterials Congress},
Pages = {670 -},
Address = {Sydney, Australia},
Year = {2004},
Keywords = {Copolymers;Polyethylene oxides;Molecular
structure;Silanes;Erosion;Supramolecular
chemistry;Crystalline materials;Inclusions;Nanostructured
materials;X ray diffraction analysis;},
Abstract = {The formation of injectable supramolecular hydrogels formed
by poly(ethylene oxide)-b-poly[(R)-3-hydroxybutyrate]-b-poly(ethylene
oxide) triblock copolymers (PEHE) and α-cyclodextrin
(α-CD) was reported. It was shown that the release
rate of the hydrogel of PEHE(50-38-50)-α-CD increases
more sharply than that of the hydrogel of
PEHE(50-55-50)-α-CD, due to the hydrolysis of
PEHE(50-38-50). It was concluded that the in vitro release
property of the gels is dependent on the structure of
copolymer. The observation suggested that the gel system
contains the necklace-like nanocrystal and its
self-assembling acts as a physical crosslinking, providing
the primary driving force for gelation of the solutions of
α-CD and the PEHE.},
Key = {05098857471}
}
@article{04158108551,
Author = {Huang, Shi-Wen and Wang, Jun and Zhang, Peng-Chi and Mao,
Hai-Quan and Zhuo, Ren-Xi and Leong, Kam
W.},
Title = {Water-soluble and nonionic polyphosphoester: Synthesis,
degradation, biocompatibility and enhancement of gene
expression in mouse muscle},
Journal = {Biomacromolecules},
Volume = {5},
Number = {2},
Pages = {306 - 311},
Year = {2004},
url = {http://dx.doi.org/10.1021/bm034241l},
Keywords = {Macromolecules;Biosynthesis;Biodegradation;Biocompatibility;Genes;Muscle;DNA;Esterification;Chlorination;Toxicity;},
Abstract = {A nonionic and water-soluble polyphosphoester,
poly(2-hydroxyethyl propylene phosphate) (PPE3), was
synthesized by chlorination of poly(4-methyl-2-oxo-2-hydro-1,3,2-dioxaphospholane),
followed by esterification with 2-benzyloxyethanol and
deprotection of the hydroxyl group by catalytic
hydrogenation in the presence of Pd-C. PPE3 degraded rapidly
in PBS 7.4 at 37 °C. The cytotoxicity and tissue
compatibility assays suggested good biocompatibility of PPE3
in vitro and in vivo. The expression of pVR1255 Luc plasmid
in mouse muscle after intramuscular (i.m.) injection of DNA
formulated with PPE3 solution in saline was enhanced up to
4-fold compared with that of naked DNA. These results
suggest the potential of this polyphosphoester for naked
DNA-based gene therapy. The advantages of this polymer
design include the biodegradability of the polyphosphoester
and its structural versatility, which allows the fine-tuning
of the physicochemical properties to optimize the
enhancement of gene expression in muscle. © 2004
American Chemical Society.},
Key = {04158108551}
}
@article{05098857971,
Author = {Li, J. and Ni, X. and Li, X. and Wang, X. and Zhou, Z. and Leong, K.W.},
Title = {A novel biodegradable amphiphilic triblock copolymer
consisting of poly[(R)-β-hydroxybutyrate] and
poly(ethylene oxide) and Its self-association
property},
Journal = {Transactions - 7th World Biomaterials Congress},
Pages = {1178 -},
Address = {Sydney, Australia},
Year = {2004},
Keywords = {Biodegradation;Polyethylene oxides;Association
reactions;Polyesters;Biopolymers;Hydrophobicity;Critical
micelle concentration;Crystalline materials;Molecular
weight;Fluorescence;Precipitation (chemical);Nuclear
magnetic resonance spectroscopy;Fourier transform infrared
spectroscopy;},
Abstract = {The synthesis of a new polyethylene oxide (PEO) PHB-PEO
triblock copolymers was discussed. It was observed that the
resulting triblock copolymers have a strong tendency toward
micelle formation in aqueous medium. The micelles formed
with the PEO-PHB-PEO triblock copolymers were stable and
readily handled. The results show the synthesis of
amphiphilic PEO-PHB-PEO triblock copolymers and their
micelle formation was unexpectedly found to be
thermosensitive.},
Key = {05098857971}
}
@article{Article,
Author = {Sun, D. D. N. and Leong, K. W.},
Title = {A Nonlinear hyperelastic mixture theory model for
anisotropy, transport, and swelling of annulus
fibrosus},
Journal = {Annals of Biomedical Engineering},
Volume = {32},
Number = {1},
Pages = {92-102},
Year = {2004},
Key = {Article}
}
@article{05098857004,
Author = {Leong, K.W. and Liao, I.C. and Yim, E. and Lim, S. and Wan,
A. and Wen, J. and Chew, S.Y. and Chua, K.N. and Ramakrishna, S. and Mao, H.Q.},
Title = {Controlled release systems designed for regenerative
medicine},
Journal = {Transactions - 7th World Biomaterials Congress},
Pages = {189 -},
Address = {Sydney, Australia},
Year = {2004},
Keywords = {Cells;Controlled drug delivery;Tissue;Biochemical
engineering;Hydrogels;Drug products;DNA;Bone;Polyelectrolytes;Synthesis
(chemical);Copolymers;Complexation;Encapsulation;Biodegradation;Ring
opening polymerization;Biocompatibility;},
Abstract = {The features of two fibrous controlled release systems where
the drug-loaded fibers are fabricated by electrospinning and
polyelectrolyte complexation (PEC) were investigated. The
controlled release behavior of drugs from the fibers
comprising the biodegradable copolymer of polycaprolactone
(PCL) and poly(ethylphosphate) (PCLEEP) was also
investigated. The copolymers were synthesized through
ring-opening polymerization of caprolactone and ethyl
ethylene phosphate (EEP). The results show that delicate
compounds such as proteins can better retain their
bioactivity in encapsulation process involving
PEC.},
Key = {05098857004}
}
@article{04198153468,
Author = {Kiang, Tina and Wen, Jie and Lim, Huay Wen and Leong, Kam
W.},
Title = {The effect of the degree of chitosan deacetylation on the
efficiency of gene transfection},
Journal = {Biomaterials},
Volume = {25},
Number = {22},
Pages = {5293 - 5301},
Year = {2004},
url = {http://dx.doi.org/10.1016/j.biomaterials.2003.12.036},
Keywords = {Genes;Acetylation;DNA;Morphology;Molecular
weight;Proteins;},
Abstract = {Chitosans with various degrees of deacetylation were
synthesized by acetylation with acetic anhydride. These
chitosans were evaluated for efficacy of nanoparticle
formation, DNA binding efficiency, morphology, and in vitro
and in vivo gene transfection efficiency. DNA binding
efficacy was reduced as degree of deacetylation was
decreased, therefore requiring an increased +/-ratio to
effect complete DNA complexation. For chitosan with a
molecular weight of 390kDa, the +/-ratio to achieve complete
DNA complexation for degrees of deacetylation of 90%, 70%
and 62% was 3.3:1, 5.0:1, and 9.0:1, respectively. The size
and morphology of these nanoparticle formulations were not
significantly different. The decreased degree of
deacetylation results in a decrease in overall luciferase
expression levels in HEK293, HeLa, and SW756 cells due to
particle destabilization in the presence of serum proteins.
However, intramuscular luciferase expression levels
increased with decreasing deacetylation over the time points
tested. Degree of chitosan deacetylation is an important
factor in chitosan-DNA nanoparticle formulation as it
affects DNA binding, release and gene transfection
efficiency in vitro and in vivo. © 2004 Elsevier Ltd.
All rights reserved.},
Key = {04198153468}
}
@article{Article,
Author = {Wan, A. C. A. and Mao, H. Q. and Wang, S. and Phua, S. H. and Lee, G. P. and Pan, J. S. and Lu, S. and Wang, J. and Leong, K. W.},
Title = {Poly(phosphoester) ionomers as tissue-engineering
scaffolds},
Journal = {Journal of Biomedical Materials Research Part B-Applied
Biomaterials},
Volume = {70B},
Number = {1},
Pages = {91-102},
Year = {2004},
Key = {Article}
}
@article{04518720255,
Author = {Wan, Andrew C. A. and Yim, Evelyn K. F. and Liao, I-Chien and Le Visage and Catherine and Leong, Kam W.},
Title = {Encapsulation of biologics in self-assembled fibers as
biostructural units for tissue engineering},
Journal = {Journal of Biomedical Materials Research - Part
A},
Volume = {71},
Number = {4},
Pages = {586 - 595},
Year = {2004},
url = {http://dx.doi.org/10.1002/jbm.a.30158},
Keywords = {Scaffolds;Encapsulation;Fibers;Cells;Proteins;},
Abstract = {The concept of a "biostructural unit" is presented as the
combination of biological and structural building blocks to
create scaffolds or constructs via a bottom-up approach.
Three types of biostructural units were constructed using
the process of fiber formation by interfacial
polyelectrolyte complexation: protein-encapsulated fiber,
ligand-immobilized fiber, and cell-encapsulated fiber units.
Water-soluble chitin (WSC) and alginate were used as the
polyelectrolyte combination to form fiber. Encapsulation and
sustained release of bovine serum albumin from the fiber
could be achieved, release profiles being dependent on the
WSC/alginate concentration ratio. Released nerve growth
factor (NGF) retained its bioactivity, as demonstrated on
PC12 cells. Biotinylated fiber could be fabricated by
biotinylating alginate before drawing fiber with WSC,
enabling biotinylated NGF to be immobilized to fiber via an
avidin bridge. The immobilized NGF induced the
differentiation of PC12 cells seeded on the fiber. Bovine
pulmonary endothelial cells, human dermal fibroblasts, and
human mesenchymal stem cells were encapsulated,
demonstrating good viability as determined by Live/Dead and
WST-1 assays. The assembly of biostructural units into
constructs was illustrated by using human mesenchymal stem
cell-encapsulated fiber units. Cells in the resulting
constructs could be induced to differentiate along
chondrogenic and osteogenic lineages. © 2004 Wiley
Periodicals, Inc.},
Key = {04518720255}
}
@article{04128068239,
Author = {Salem, Aliasger K. and Chao, Johnny and Leong, Kam W. and Searson, Peter C.},
Title = {Receptor-mediated self-assembly of multi-component magnetic
nanowires},
Journal = {Advanced Materials},
Volume = {16},
Number = {3},
Pages = {268 - 271},
Year = {2004},
url = {http://dx.doi.org/10.1002/adma.200305700},
Keywords = {Ferromagnetic materials;Crystal orientation;Gold;Nickel;Synthesis
(chemical);Scanning electron microscopy;Optical
microscopy;Silver;Alumina;Suspensions (fluids);Substrates;Solutions;},
Abstract = {The directed orientation of ferromagnetic nanowires tethered
to spatially controlled regions of a surface is reported. A
light microscope image of 9 μm-long, two-segment Au/Ni
nanowires with a biotinylated Au segment tethered to
patterned avidin tracks is described. The aspect ratio of
the nickel segments is -50, so the magnetic easy axis is
parallel to the wire axis. The nanowires have rotated to be
parallel to an applied magnetic field.},
Key = {04128068239}
}
@article{05349317215,
Author = {Salem, Aliasger K. and Searson, Peter C. and Leong, Kam
W.},
Title = {Multifunctional nanorods for gene delivery},
Journal = {Materials Research Society Symposium Proceedings},
Volume = {EXS},
Number = {1},
Pages = {455 - 457},
Address = {Boston, MA, United States},
Year = {2004},
Keywords = {Genetic engineering;Drug products;Genes;Synthesis
(chemical);Gold compounds;Electrochemistry;Etching;Cell
membranes;DNA;Energy dispersive spectroscopy;Transmission
electron microscopy;Ultraviolet spectroscopy;},
Abstract = {The potential of multi-segment metallic nanorods in gene
delivery system were investigated to achieve the control of
size and composition by inorganic synthesis. Au/Ni nanorods
were deposited by template synthesis method, which involved
electrochemical deposition into a non-conducting membrane
with an array of cylindrical pores. The nanorods were then
used for the synthesis of a wide range of materials and
structures. The unique properties of the nanorods that allow
for defined aspect ratios and the addition of magnetic
segments were utilized as a probe to determine the effects
and inter-relationships of size, magnetism and cell
targeting proteins in gene delivery.},
Key = {05349317215}
}
@article{04088030492,
Author = {Wang, Jun and Sun, Daniel N. and Shin-ya, Yoshitsune and Leong, Kam W.},
Title = {Stimuli-responsive hydrogel based on poly(propylene
phosphate)},
Journal = {Macromolecules},
Volume = {37},
Number = {2},
Pages = {670 - 672},
Year = {2004},
url = {http://dx.doi.org/10.1021/ma035453d},
Keywords = {Hydrogels;Phase transitions;Synthesis (chemical);Biodegradation;Biocompatibility;Rheology;Shear
stress;Temperature;Elastic moduli;Gel permeation
chromatography;Nuclear magnetic resonance
spectroscopy;},
Abstract = {Poly(propylene phosphate) solutions were studied and found
to display a sol-gel transition temperature that can be
controlled by adjusting the concentrations of polymer and
Ca<sup>2+</sup> so that the therapeutic delivery cargo is
liquid at room temperature but solidifies at the in vivo
temperature of 37°C. The gels showed rapid gelation
kinetics but instability at high shear strains. Ion exchange
between buffer and gel induced a dissociation of the network
with time, leading to a zero-order controlled release of
plasmid DNA or lysozyme.},
Key = {04088030492}
}
@article{04298267389,
Author = {Wan, Andrew C. A. and Mao, Hai-Quan and Wang, Shu and Phua,
Su Hui and Lee, Gin Ping and Pan, Jisheng and Lu, Shen and Wang, Jun and Leong, Kam W.},
Title = {Poly(phosphoester) ionomers as tissue-engineering
scaffolds},
Journal = {Journal of Biomedical Materials Research - Part B Applied
Biomaterials},
Volume = {70},
Number = {1},
Pages = {91 - 102},
Year = {2004},
Keywords = {Scaffolds;Tissue;Biodegradation;Elastic moduli;Polymers;Strain;Glass
transition;Indentation;Biomaterials;Fourier transform
infrared spectroscopy;Absorption;},
Abstract = {Regenerative medicine requires scaffolds of divergent
physicochemical properties for different tissue-engineering
applications. To this end, a series of biodegradable
poly-(phosphoester) ionomers of the general composition
[p(BHET-EOP-HOP/TC)] was synthesized, with BHET(bis-hydroxyl
ethylene phosphate):EOP(ethylene phosphate):HOP(free
phosphate) ratios of 60:20:20, 70:10:20, and 75:5:20,
respectively. The 60/20/20 ionomer possessed the best
tensile properties, exhibiting an average tensile modulus of
68 MPa and strain at break of 31%. Calcium treatment of the
ionomer films led to significantly higher hardness and
elastic moduli as measured by indentation. Calcium binding
was evident from the increase in glass transition and
melting temperatures, and a shift in the P->O absorption
in the FTIR spectrum. Stable N-hydroxysuccinimide ester
(NHS) of the ionomers could be synthesized to facilitate
derivatization, as demonstrated by conjugation of GRGDS in
this study. The polymers conjugated with NHS were hydrolyzed
in a biphasic mode, with a fast initial phase occurring in
the first few hours, followed by a slower phase in the next
few days. These ionomers represent a novel class of
biomaterials with readily controllable physical and chemical
attributes for tissue engineering. © 2004 Wiley
Periodicals, Inc.},
Key = {04298267389}
}
@article{05098857695,
Author = {Feng, Q. and Jiang, X.S. and Chai, C. and Lim, W.S. and Leong, K.W. and Mao, H.Q.},
Title = {Ex vivo expansion of hematopoietic primitive cells on ECM
molecule-immobilized scaffold},
Journal = {Transactions - 7th World Biomaterials Congress},
Pages = {898 -},
Address = {Sydney, Australia},
Year = {2004},
Keywords = {Cell immobilization;Bone;Collagen;Polyethylene
terephthalates;Transplantation (surgical);Medical
problems;Disease control;Cell membranes;Solubility;Suspensions
(fluids);pH effects;Crosslinking;},
Abstract = {The ex vivo expansion of hematopoietic stem sells (HSC) on
extracellular matrix (ECM) molecule-immobilized scaffold was
investigated. The scaffold used was a fibronectin and
collagen conjugated polyethylene terephthalate (PET)
scaffold. Bone marrow CD34+ cells were cultured in the
modified PET scaffolds in a 96-well plate using serum free
StemSpam medium supplemented with cytokines. It was observed
that the scaffolds surface-conjugated with ECM molecules
served as an effective substrate for the expansion of
hematopoietic primitive cells. Fibronectin conjugated
scaffold was found to exhibit the highest extent of CD34+
cell expansion.},
Key = {05098857695}
}
@article{05098857143,
Author = {Quek, C.H. and Li, J. and Sun, T. and Chan, M.L.H. and Mao,
H.Q. and Gan, L.M. and Leong, K.W. and Yu,
H.},
Title = {Photo-crosslinkable microcapsules formed by polyelectrolyte
copolymer and modified collagen for rat hepatocyte
encapsulation},
Journal = {Transactions - 7th World Biomaterials Congress},
Pages = {330 -},
Address = {Sydney, Australia},
Year = {2004},
Keywords = {Polyelectrolytes;Collagen;Crosslinking;Encapsulation;Polymethyl
methacrylates;Polystyrenes;Urea;Antibodies;Chemical
reactors;Immunology;Precipitation (chemical);Polymerization;Synthesis
(chemical);Calorimetry;},
Abstract = {New anionic polyelectrolyte tetra-copolymers based on methyl
methacrylate (MMA), 2-hydroxyethyl methacrylate (HEMA),
methacrylic acid (MAA) and a photo-crosslinkable
4-(4-methoxycinnamoyl) phenyl methacrylate monomer (MeOCPMA)
were synthesized. Photo-crosslinkable microcapsules were
formed by complex coacervation reaction of modified collagen
that constituted the inner core with the tetra-copolymers as
the outer photo-crosslinkable copolymer shell. Upon
photo-crosslinking of the microcapsules with uv-vis light
irradiation, the mechanical strength of these microcapsules
was dramatically strengthened. The cellular functions of the
encapsulated hepatocytes were also enhanced. These new
photo-crosslinkable tetra-copolymer formulations have opened
a way to the development of hepatocyte microencapsulation
technology for bioartificial liver assist device
(BLAD).},
Key = {05098857143}
}
@article{04138076209,
Author = {Quek, Chai-Hoon and Li, Jun and Sun, Tao and Chan, Melinda
Ling Hou and Mao, Hai-Quan and Gan, Leong Ming and Leong,
Kam W. and Yu, Hanry},
Title = {Photo-crosslinkable microcapsules formed by polyelectrolyte
copolymer and modified collagen for rat hepatocyte
encapsulation},
Journal = {Biomaterials},
Volume = {25},
Number = {17},
Pages = {3531 - 3540},
Year = {2004},
url = {http://dx.doi.org/10.1016/j.biomaterials.2003.09.112},
Keywords = {Crosslinking;Copolymers;Polyelectrolytes;Collagen;Biosynthesis;},
Abstract = {New anionic polyelectrolyte tetra-copolymers with
photo-crosslinkable 4-(4-methoxycinnamoyl)phenyl
methacrylate monomer in addition to a HEMA-MMA-MAA
ter-copolymer system were synthesized. The tetra-copolymers
were used to form photo-crosslinkable microcapsules with
modified collagen by complex coacervation for rat
hepatocytes encapsulation. The hepatocytes were encapsulated
within a two-layered membrane comprising of modified
collagen as the inner core and an outer photo-crosslinkable
copolymer shell. Upon photo-crosslinking of the
microcapsules with UV-Vis light irradiation, the mechanical
strength and chemical stability of the microcapsules, and
the cellular functions of the encapsulated hepatocytes were
enhanced. Particularly, the mechanical stability of the
microcapsules was dramatically strengthened. The new
photo-crosslinkable tetra-copolymer formulation described in
this article has opened a way to the development of
hepatocyte microencapsulation technology for bioartifical
liver assist device. © 2003 Elsevier Ltd. All rights
reserved.},
Key = {04138076209}
}
@article{04398376781,
Author = {Li, Xu and Li, Jun and Leong, Kam W.},
Title = {Role of intermolecular interaction between hydrophobic
blocks in block-selected inclusion complexation of
amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene
oxide) triblock copolymers with cyclodextrins},
Journal = {Polymer},
Volume = {45},
Number = {20},
Pages = {6845 - 6851},
Year = {2004},
url = {http://dx.doi.org/10.1016/j.polymer.2004.07.038},
Keywords = {Polyethylene oxides;Complexation;Hydrophobicity;X ray
diffraction analysis;Differential scanning
calorimetry;Nuclear magnetic resonance;High temperature
effects;},
Abstract = {The influence of hydrophobic interaction between poly[(R)-3-
hydroxybutyrate] blocks on block-selected inclusion
complexation between amphiphilic poly(ethylene
oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide))
(PEO-PHB-PEO) triblock copolymers and α-cyclodextrin
(α-CD) or γ-cyclodextrin (γ-CD) was
studied by X-ray diffraction, differential scanning
calorimetry (DSC), FTIR and <sup>1</sup>H NMR. Due to the
stronger hydrophobic interaction at higher temperature, the
amphiphilic triblock copolymer tends to aggregate to form
tighter core-shell sphere with PHB block in the core and PEO
in the corona. Therefore, the CD threaded onto PEO blocks
cannot further slide onto the PHB block, which resulted in a
highly block-selected inclusion complex formation. Moreover,
the DSC results indicated that the triblock copolymer
coalesced from its ICs with hot water showed an increase in
microphase separation compared with the as-synthesized
triblock copolymer, which further supports our hypothesis
that CD only selectively includes PEO blocks of the triblock
copolymer at higher temperature. © 2004 Elsevier Ltd.
All rights reserved.},
Key = {04398376781}
}
@article{Article,
Author = {Salem, A. K. and Chao, J. and Leong, K. W. and Searson, P.
C.},
Title = {Receptor-mediated self-assembly of multi-component magnetic
nanowires},
Journal = {Advanced Materials},
Volume = {16},
Number = {3},
Pages = {268-+},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Le Visage and C. and Dunham, B. and Flint, P. and Leong, K.
W.},
Title = {Coculture of mesenchymal stem cells and respiratory
epithelial cells to engineer a human composite respiratory
mucosa},
Journal = {Tissue Engineering},
Volume = {10},
Number = {9-10},
Pages = {1426-1435},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Wen, J. and Mao, H. Q. and Li, W. P. and Lin, K. Y. and Leong, K. W.},
Title = {Biodegradable polyphosphoester micelles for gene
delivery},
Journal = {Journal of Pharmaceutical Sciences},
Volume = {93},
Number = {8},
Pages = {2142-2157},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Chan, V. and Liu, K. K. and Le Visage and C. and Ju, B. F. and Leong, K. W.},
Title = {Bioadhesive characterization of poly(methylidene malonate
2.12) microparticle on model extracellular
matrix},
Journal = {Biomaterials},
Volume = {25},
Number = {18},
Pages = {4327-4332},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Wang, J. and Sun, D. D. N. and Shin-ya, Y. and Leong, K.
W.},
Title = {Stimuli-responsive hydrogel based on poly(propylene
phosphate)},
Journal = {Macromolecules},
Volume = {37},
Number = {2},
Pages = {670-672},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Huang, S. W. and Wang, J. and Zhang, P. C. and Mao, H. Q. and Zhuo, R. X. and Leong, K. W.},
Title = {Water-soluble and nonionic polyphosphoester: Synthesis,
degradation, biocompatibility and enhancement of gene
expression in mouse muscle},
Journal = {Biomacromolecules},
Volume = {5},
Number = {2},
Pages = {306-311},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Quek, C. H. and Li, J. and Sun, T. and Ling, M. and Chan, H. and Mao, H. Q. and Gan, L. M. and Leong, K. W. and Yu,
H.},
Title = {Photo-crosslinkable microcapsules formed by polyelectrolyte
copolymer and modified collagen for rat hepatocyte
encapsulation},
Journal = {Biomaterials},
Volume = {25},
Number = {17},
Pages = {3531-3540},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Wang, J. and Gao, S. J. and Zhang, P. C. and Wang, S. and Mao, M. Q. and Leong, K. W.},
Title = {Polyphosphoramidate gene carriers: effect of charge group on
gene transfer efficiency},
Journal = {Gene Therapy},
Volume = {11},
Number = {12},
Pages = {1001-1010},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Bini, T. B. and Gao, S. J. and Xu, X. Y. and Wang, S. and Ramakrishna, S. and Leong, K. W.},
Title = {Peripheral nerve regeneration by microbraided
poly(L-lactide-co-glycolide) biodegradable polymer
fibers},
Journal = {Journal of Biomedical Materials Research Part
A},
Volume = {68A},
Number = {2},
Pages = {286-295},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Wang, J. and Lee, I. L. and Lim, W. S. and Chia, S. M. and Yu, H. and Leong, K. W. and Mao, H. Q.},
Title = {Evaluation of collagen and methylated collagen as gene
carriers},
Journal = {International Journal of Pharmaceutics},
Volume = {279},
Number = {1-2},
Pages = {115-126},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Wan, A. C. A. and Liao, I. C. and Yim, E. K. F. and Leong,
K. W.},
Title = {Mechanism of fiber formation by interfacial polyelectrolyte
complexation},
Journal = {Macromolecules},
Volume = {37},
Number = {18},
Pages = {7019-7025},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Li, Q. and Williams, C. G. and Sun, D. D. N. and Wang, J. and Leong, K. and Elisseeff, J. H.},
Title = {Photocrosslinkable polysaccharides based on chondroitin
sulfate},
Journal = {Journal of Biomedical Materials Research Part
A},
Volume = {68A},
Number = {1},
Pages = {28-33},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Shin-Ya, Y. and Tsurushima, H. and Tsurumi, T. and Kajiuchi,
T. and Leong, K. W.},
Title = {Polyelectrolyte complex films derived from
polyethyleneoxide-maleic acid copolymer and chitosan:
Preparation and characterization},
Journal = {Macromolecular Bioscience},
Volume = {4},
Number = {5},
Pages = {526-531},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Kiang, T. and Bright, C. and Cheung, C. Y. and Stayton, P.
S. and Hoffman, A. S. and Leong, K. W.},
Title = {Formulation of chitosan-DNA nanoparticles with poly(propyl
acrylic acid) enhances gene expression},
Journal = {Journal of Biomaterials Science-Polymer Edition},
Volume = {15},
Number = {11},
Pages = {1405-1421},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Kiang, T. and Wen, H. and Lim, H. W. and Leong, K.
W.},
Title = {The effect of the degree of chitosan deacetylation on the
efficiency of gene transfection},
Journal = {Biomaterials},
Volume = {25},
Number = {22},
Pages = {5293-5301},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Salem, A. K. and Chen, M. and Hayden, J. and Leong, K. W. and Searson, P. C.},
Title = {Directed assembly of multisegment Au/Pt/Au
nanowires},
Journal = {Nano Letters},
Volume = {4},
Number = {6},
Pages = {1163-1165},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Le Visage and C. and Rioux-Leclercq, N. and Haller, M. and Breton, P. and Malavaud, B. and Leong, K.},
Title = {Efficacy of paclitaxel released from bio-adhesive polymer
microspheres on model superficial bladder
cancer},
Journal = {Journal of Urology},
Volume = {171},
Number = {3},
Pages = {1324-1329},
Year = {2004},
Key = {Article}
}
@article{Article,
Author = {Wan, A. C. A. and Yim, E. K. F. and Liao, I. C. and Le
Visage, C. and Leong, K. W.},
Title = {Encapsulation of biologics in self-assembled fibers as
biostructural units for tissue engineering},
Journal = {Journal of Biomedical Materials Research Part
A},
Volume = {71A},
Number = {4},
Pages = {586-595},
Year = {2004},
Key = {Article}
}
@article{8216781,
Author = {Salem, A.K. and Min Chen and Hayden, J. and Leong, K.W. and Searson, P.C.},
Title = {Directed assembly of multisegment Au/Pt/Au
nanowires},
Journal = {Nano Lett. (USA)},
Volume = {4},
Number = {6},
Pages = {1163 - 5},
Year = {2004},
url = {http://dx.doi.org/10.1021/nl049462r},
Keywords = {gold;molecular biophysics;monolayers;nanowires;platinum;self-assembly;},
Abstract = {We demonstrate directed end-to-end assembly of Au/Pt/Au
multisegment nanowires using the biotin/avidin linkage. The
formation of a self-assembled monolayer on the central
platinum segments is essential to avoid nonspecific binding
of the linker group and hence to minimize lateral
assembly},
Key = {8216781}
}
@article{8103476,
Author = {Faranesh, A.Z. and Nastley, M.T. and de la Cruz, C.P. and Haller, M.F. and Laquerriere, P. and Leong, K.W. and McVeigh, E.R.},
Title = {In vitro release of vascular endothelial growth factor from
gadolinium-doped biodegradable microspheres},
Journal = {Magn. Reson. Med. (USA)},
Volume = {51},
Number = {6},
Pages = {1265 - 71},
Year = {2004},
url = {http://dx.doi.org/10.1002/mrm.20092},
Keywords = {biochemistry;biomedical MRI;blood vessels;drug delivery
systems;electron microscopy;encapsulation;gadolinium;molecular
biophysics;polymers;prosthetics;proteins;},
Abstract = {A drug delivery vehicle was constructed that could be
visualized noninvasively with MRI. The biodegradable polymer
poly(DL-lactic-co-glycolic acid) (PLGA) was used to
fabricate microspheres containing vascular endothelial
growth factor (VEGF) and the MRI contrast agent gadolinium
diethylenetriamine pentaacetic acid (Gd-DTPA). The
microspheres were characterized in terms of size, drug and
contrast agent encapsulation, and degradation rate. The PLGA
microspheres had a mean diameter of 48±18 μm. The
gadolinium loading was 17±3 μg/mg polymer and the
VEGF loading was 163±22 ng/mg polymer. Electron
microscopy revealed that the Gd was dispersed throughout the
microspheres and it was confirmed that the Gd loading was
sufficient to visualize the microspheres under MRI. VEGF and
Gd-DTPA were released from the microspheres in vitro over a
period of ~6 weeks in three phases: a burst, followed by a
slow steady-state, then a rapid steady-state. Biodegradable
Gd-doped microspheres can be effectively used to deliver
drugs in a sustained manner, while being monitored
noninvasively with MRI},
Key = {8103476}
}
@article{7875313,
Author = {Salem, A.K. and Searson, P.C. and Leong,
K.W.},
Title = {Multifunctional nanorods for gene delivery},
Journal = {Nature Mater. (UK)},
Volume = {2},
Number = {10},
Pages = {668 - 71},
Year = {2003},
url = {http://dx.doi.org/10.1038/nmat974},
Keywords = {cellular transport;DNA;genetics;gold;molecular
biophysics;nanostructured materials;nickel;patient
treatment;},
Abstract = {The goal of gene therapy is to introduce foreign genes into
somatic cells to supplement defective genes or provide
additional biological functions, and can be achieved using
either viral or synthetic non-viral delivery systems.
Compared with viral vectors, synthetic gene-delivery
systems, such as liposomes and polymers, offer several
advantages including ease of production and reduced risk of
cytotoxicity and immunogenicity, but their use has been
limited by the relatively low transfection efficiency. This
problem mainly stems from the difficulty in controlling
their properties at the nanoscale. Synthetic inorganic gene
carriers have received limited attention in the gene-therapy
community, the only notable example being gold nanoparticles
with surface-immobilized DNA applied to intradermal genetic
immunization by particle bombardment. Here we present a
non-viral gene-delivery system based on multisegment
bimetallic nanorods that can simultaneously bind compacted
DNA plasmids and targeting ligands in a spatially defined
manner. This approach allows precise control of composition,
size and multifunctionality of the gene-delivery system.
Transfection experiments performed in vitro and in vivo
provide promising results that suggest potential in genetic
vaccination applications},
Key = {7875313}
}
@article{Article,
Author = {Liu, X. M. and Yang, Y. Y. and Leong, K.
W.},
Title = {Thermally responsive polymeric micellar nanoparticles
self-assembled from cholesteryl end-capped random
poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide):
synthesis, temperature-sensitivity, and morphologies},
Journal = {Journal of Colloid and Interface Science},
Volume = {266},
Number = {2},
Pages = {295-303},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Li, J. and Li, X. and Ni, X. P. and Leong, K.
W.},
Title = {Synthesis and characterization of new biodegradable
amphiphilic poly(ethylene oxide)-b-poly[(R)-3-hydroxy
butyratel-b-poly(ethylene oxide) triblock
copolymers},
Journal = {Macromolecules},
Volume = {36},
Number = {8},
Pages = {2661-2667},
Year = {2003},
Key = {Article}
}
@article{03437689566,
Author = {Lu, Hong-Fang and Lim, Wei Seng and Wang, Jun and Tang,
Zhi-Qun and Zhang, Peng-Chi and Leong, Kam W. and Chia, Ser
Mien and Yu, Hanry and Mao, Hai-Quan},
Title = {Galactosylated PVDF membrane promotes hepatocyte attachment
and functional maintenance},
Journal = {Biomaterials},
Volume = {24},
Number = {27},
Pages = {4893 - 4903},
Year = {2003},
url = {http://dx.doi.org/10.1016/S0142-9612(03)00404-6},
Keywords = {Adsorption;Hydrophobicity;Density (specific
gravity);Solutions;Collagen;Substrates;},
Abstract = {One of the major challenges in BLAD design is to develop
functional substrates suitable for hepatocyte attachment and
functional maintenance. In the present study, we designed a
poly(vinylidene difluoride) (PVDF) surface coated with
galactose-tethered Pluronic polymer. The galactose-derived
Pluronic F68 (F68-Gal) was adsorbed on PVDF membrane through
hydrophobic-hydrophobic interaction between PVDF and the
polypropylene oxide segment in Pluronic. The galactose
density on the modified PVDF surface increased with the
concentration of the F68-Gal solution, reaching 15.4nmol
galactosyl groups per cm<sup>2</sup> when a 1mg/ml of
F68-Gal solution was used. The adsorbed F68-Gal remained
relatively stable in culture medium. Rat hepatocytes
attachment efficiency on F68-Gal modified PVDF membrane was
similar to that on collagen-coated surface. The attached
hepatocytes on PVDF/F68-Gal membrane self-assembled into
multi-cellular spheroids after 1 day of culture. These
attached hepatocytes in spheroids exhibited higher cell
functions such as albumin synthesis and P450 1A1
detoxification function compared to unmodified PVDF membrane
and collagen-coated surface. These results suggest the
potential of this galactose-immobilized PVDF membrane as a
suitable substrate for hepatocyte culture. © 2003
Elsevier Ltd. All rights reserved.},
Key = {03437689566}
}
@article{03107384819,
Author = {Li, Jun and Ni, Xiping and Zhou, Zhihan and Leong, Kam
W.},
Title = {Preparation and characterization of polypseudorotaxanes
based on block-selected inclusion complexation between
poly(propylene oxide)-poly(ethylene oxide)-poly(propylene
oxide) triblock copolymers and α-cyclodextrin},
Journal = {Journal of the American Chemical Society},
Volume = {125},
Number = {7},
Pages = {1788 - 1795},
Year = {2003},
url = {http://dx.doi.org/10.1021/ja026623p},
Keywords = {Complexation;Stoichiometry;Glass transition;Differential
scanning calorimetry;X ray diffraction analysis;Thermogravimetric
analysis;Nuclear magnetic resonance spectroscopy;},
Abstract = {A series of new polypseudorotaxanes were synthesized in high
yields when the middle poly(ethylene oxide) (PEO) block of
poly(propylene oxide)-poly (ethylene oxide)-poly(propylene
oxide) (PPO-PEO-PPO) triblock copolymers was selectively
recognized and included by α-cyclodextrin (α-CD)
to form crystalline inclusion complexes (ICs), although the
middle PEO block was flanked by two thicker PPO blocks, and
a PPO chain had been previously thought to be impenetrable
to α-CD. X-ray diffraction studies demonstrated that
the IC domains of the polypseudorotaxanes assumed a
channel-type structure similar to the necklace-like ICs
formed by α-CD and PEO homopolymers. Solid-state
CP/MAS <sup>13</sup>C NMR studies showed that the α-CD
molecules in the polypseudorotaxanes adopted a symmetrical
conformation due to the formation of ICs. The compositions
and stoichiometry of the polypseudorotaxanes were studied
using <sup>1</sup>H NMR, and a 2:1 (ethylene oxide unit to
α-CD) stoichiometry was found for all
polypseudorotaxanes although the PPO-PEO-PPO triblock
copolymers had different compositions and block lengths,
suggesting that only the PEO block was closely included by
α-CD molecules, whereas the PPO blocks were uncovered.
The hypothesis was further supported by the differential
scanning calorimetry (DSC) studies of the
polypseudorotaxanes. The glass transitions of the PPO blocks
in the polypseudorotaxanes were clearly observed because
they were uncovered by α-CD and remained amorphous,
whereas the glass-transition temperatures increased, because
the molecular motion of the PPO blocks was restricted by the
hard crystalline phases of the IC domains formed by
α-CD and the PEO blocks. The thermogravimetric
analysis (TGA) revealed that the polypseudorotaxanes had
better thermal stability than their free components due to
the inclusion complexation. Finally, the kinetics of the
threading process of α-CD onto the copolymers was also
studied. The findings reported in this article suggested
interesting possibilities in designing other cyclodextrin
ICs and polypseudorotaxanes with block structures.},
Key = {03107384819}
}
@article{7832981,
Author = {Chao Yin and Ser Mien Chia and Chai Hoon Quek and Hanry Yu and Ren-Xi Zhuo and Leong, K.W. and Hai-Quan
Mao},
Title = {Microcapsules with improved mechanical stability for
hepatocyte culture},
Journal = {Biomaterials (UK)},
Volume = {24},
Number = {10},
Pages = {1771 - 80},
Year = {2003},
url = {http://dx.doi.org/10.1016/S0142-9612(02)00580-X},
Keywords = {bioreactors;cellular biophysics;encapsulation;liver;mechanical
stability;polymerisation;polymers;proteins;yield
stress;},
Abstract = {Packed-bed or fluidized-bed bioreactor filled with
microencapsulated hepatocytes has been proposed as one of
the promising designs for bioartificial liver assist device
(BLAD) because of potential advantages of high mass
transport rate and optimal microenvironment for hepatocyte
culture. Recently, we have developed a microcapsule system
for the encapsulation of hepatocytes. The microcapsules
consist of an inner core of modified collagen and an outer
shell of terpolymer of methyl methacrylate, methacrylate and
hydroxyethyl methacrylate. Cells encapsulated in these
microcapsules exhibit enhanced cellular functions. Improving
the mechanical stability of the microcapsules to withstand
the shear stress induced by high perfusion rate would be
crucial to the success of BLAD applications. In this study,
we investigated the effects of terpolymer molecular weight
(M<sub>W</sub>) on the mechanical property of these
microcapsules and the differentiated functions of
encapsulated hepatocytes. Six terpolymers with different
M<sub>W</sub> were synthesized using radical polymerization
in solution by adjusting the reaction temperature and the
initiator concentration. All the terpolymers formed
microcapsules with the methylated collagen. While the
terpolymer M<sub>W</sub> had little effect on the capsule
membrane thickness and permeability of serum albumin, the
mechanical property of the microcapsules was significantly
improved by the higher M<sub>W</sub> of the terpolymer.
Differential functions of the hepatocytes cultured in the
microcapsules, including urea synthesis, albumin synthesis
and cytochrome P450 metabolic activity, were not
significantly affected by the terpolymer
M<sub>W</sub>},
Key = {7832981}
}
@article{03527792547,
Author = {Li, Jun and Ni, Xiping and Leong, Kam W.},
Title = {Injectable drug-delivery systems based on supramolecular
hydrogels formed by poly(ethylene oxide)s and
α-cyclodextrin},
Journal = {Journal of Biomedical Materials Research - Part
A},
Volume = {65},
Number = {2},
Pages = {196 - 202},
Year = {2003},
url = {http://dx.doi.org/10.1002/jbm.a.10444},
Keywords = {Supramolecular chemistry;Hydrogels;Polyethylene
oxides;Implants (surgical);Biocompatibility;Proteins;Crosslinking;Gelation;Drug
products;Sorption;Molecular weight;Thermal effects;X ray
diffraction analysis;},
Abstract = {Polymeric hydrogels long have attracted interest for
biomaterials applications because of their generally
favorable biocompatibility. High in water content, they are
particularly attractive for delivery of delicate bioactive
agents, such as proteins. However, because they require
covalent crosslinking for gelation, many hydrogels can be
applied only as implantables, and incorporation of drugs by
sorption may be time-consuming and limiting with regard to
the loading level. Therefore a delivery formulation where
gelation and drug loading can be achieved simultaneously,
taking place in an aqueous environment and without covalent
crosslinking, would be attractive. Herein is described a new
class of injectable and bioabsorbable supramolecular
hydrogels formed from poly(ethylene oxide)s (PEOs) and
α-cyclodextrin (α-CD) for controlled drug
delivery. The hydrogel formation is based on physical
crosslinking induced by supramolecular self-assembling with
no chemical crosslinking reagent involved. The
supramolecular structure of the hydrogels was confirmed with
wide-angle X-ray diffraction studies. The gelation kinetics
was found to be dependent on the concentrations of the
polymer and α-CD as well as on the molecular weight of
the PEO used. The rheologic studies of the hydrogels showed
that the hydrogels were thixotropic and reversible and that
they could be injected through fine needles. The components
of the supramolecular hydrogels potentially are
biocompatible and nontoxic. Drugs can be encapsulated
directly into the hydrogels in situ at room temperature
without any contact with organic solvents. The
supramolecular hydrogels were evaluated in terms of their in
vitro release kinetics. The rate-controlling mechanism of
macromolecular drug release might be the erosion of the
hydrogels. © 2003 Wiley Periodicals,
Inc.},
Key = {03527792547}
}
@article{Article,
Author = {Xu, X. Y. and Yee, W. C. and Hwang, P. Y. K. and Yu, H. and Wan, A. C. A. and Gao, S. J. and Boon, K. L. and Mao, H. Q. and Leong, K. W. and Wang, S.},
Title = {Peripheral nerve regeneration with sustained release of
poly(phosphoester) microencapsulated nerve growth factor
within nerve guide conduits},
Journal = {Biomaterials},
Volume = {24},
Number = {13},
Pages = {2405-2412},
Year = {2003},
Key = {Article}
}
@article{03127401645,
Author = {Li, Xu and Li, Jun and Leong, Kam W.},
Title = {Preparation and characterization of inclusion complexes of
biodegradable amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene
oxide) triblock copolymers with cyclodextrins},
Journal = {Macromolecules},
Volume = {36},
Number = {4},
Pages = {1209 - 1214},
Year = {2003},
url = {http://dx.doi.org/10.1021/ma0213347},
Keywords = {Biodegradation;Inclusions;Copolymers;Solutions;Structure
(composition);Integrated circuits;X ray diffraction
analysis;Nuclear magnetic resonance;Fourier transform
infrared spectroscopy;},
Abstract = {Inclusion complexes (ICs) of biodegradable amphiphilic
poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene
oxide) triblock copolymers with α-cyclodextrin
(α-CD) or γ-cyclodextrin (γ-CD) were
prepared from aqueous medium. The ICs were characterized by
XRD, DSC, <sup>13</sup>C CP/MAS NMR, <sup>1</sup>H NMR,
FTIR, and TGA. The results of XRD and <sup>13</sup>C CP/MAS
NMR indicated that the ICs formed channel structure, and the
α-CD or γ-CD molecules in the ICs adopted a more
symmetric conformation compared with their uncomplexed
states. As to the triblock copolymers, while the
poly(ethylene oxide) blocks were included in the channel
structure, the poly[(R)-3-hydroxybutyrate] block was
partially threaded by α-CD or γ-CD, which was
confirmed by the results of XRD, DSC, <sup>1</sup>H NMR, and
FTIR. The formation of ICs led to an increase in the thermal
stability of both cyclodextrins and the triblock
copolymers.},
Key = {03127401645}
}
@article{03527792848,
Author = {Yin, Chao and Ying, Lei and Zhang, Peng-Chi and Zhuo, Ren-Xi and Kang, En-Tang and Leong, Kam W. and Mao,
Hai-Quan},
Title = {High density of immobilized galactose ligand enhances
hepatocyte attachment and function},
Journal = {Journal of Biomedical Materials Research - Part
A},
Volume = {67},
Number = {4},
Pages = {1093 - 1104},
Year = {2003},
url = {http://dx.doi.org/10.1002/jbm.a.10033},
Keywords = {Collagen;Polyethylene terephthalates;Grafting
(chemical);Ultraviolet radiation;Irradiation;Substrates;Synthesis
(chemical);},
Abstract = {Galactosylated surface is an attractive substrate for
hepatocyte culture because of the specific interaction
between the galactose ligand and the asialoglycoprotein
receptor on hepatocytes. In this study, we described a
scheme to achieve high density of immobilized galactose
ligands on polyethylene terephthalate (PET) surface by first
surface-grafting polyacrylic acid on plasma-pretreated PET
film under UV irradiation, followed by conjugation of a
galactose derivative (1-O-(6 prime -aminohexyl)-D-galactopyranoside)
to the grafted polyacrylic acid chains. A high galactose
density of 513 nmol/cm <sup>2</sup> on the PET surface was
used in this study to investigate the behavior of cultured
hepatocyte. This engineered substrate showed high affinity
to fluorescein isothiocyanate-lectin binding. Primary rat
hepatocytes, when seeded at a density of 2 x 10<sup>5</sup>
cells/cm<sup>2</sup>, attached to the galactosylated PET
substrate at a similar efficiency compared with
collagen-coated substrate. The hepatocytes spontaneously
formed aggregates 1 day after cell seeding and showed better
maintenance of albumin secretion and urea synthesis
functions than those cultured on collagen-coated surface.
© 2003 Wiley Periodicals, Inc.},
Key = {03527792848}
}
@article{03197464802,
Author = {Li, Jun and Li, Xu and Ni, Xiping and Leong, Kam
W.},
Title = {Synthesis and characterization of new biodegradable
amphiphilic poly(ethylene oxide)-b-poly [(R)-3-hydroxy
butyrate]-b-poly(ethylene oxide) triblock
copolymers},
Journal = {Macromolecules},
Volume = {36},
Number = {8},
Pages = {2661 - 2667},
Year = {2003},
url = {http://dx.doi.org/10.1021/ma025725x},
Keywords = {Synthesis (chemical);Biodegradation;Hydrophobicity;Molecular
weight;Precipitation (chemical);X ray diffraction;Thermogravimetric
analysis;Differential scanning calorimetry;Nuclear magnetic
resonance spectroscopy;Fourier transform infrared
spectroscopy;},
Abstract = {Biodegradable amphiphilic poly(ethylne oxide)
(PEO)-poly[(R)-3-hydroxy butyrate] (PHB)-PEO triblock
copolymers were synthesized. Two chains of PEO were coupled
with a low-molecular weight isotactic PHB chain in the
middle. The structures and molecular characteristics of the
PEO-PHB-PEO triblock copolymers were studied by gel
permeation chromatography (GPC), nuclear magnetic resonance
(NMR) and fourier transform infrared spectroscopy
(FTIR).},
Key = {03197464802}
}
@article{Article,
Author = {Wen, J. and Kim, G. J. A. and Leong, K. W.},
Title = {Poly(D,Llactide-co-ethyl ethylene phosphate)s as new drug
carriers},
Journal = {Journal of Controlled Release},
Volume = {92},
Number = {1-2},
Pages = {39-48},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Yin, C. and Chia, S. M. and Quek, C. H. and Yu, H. R. and Zhuo, R. X. and Leong, K. W. and Mao, H.
Q.},
Title = {Microcapsules with improved mechanical stability for
hepatocyte culture},
Journal = {Biomaterials},
Volume = {24},
Number = {10},
Pages = {1771-1780},
Year = {2003},
Key = {Article}
}
@article{03177447491,
Author = {Xu, Xiaoyun and Yee, Woon-Chee and Hwang, Peter Y.K. and Yu,
Hanry and Wan, Andrew C.A. and Gao, Shujun and Boon,
Kum-Loong and Mao, Hai-Quan and Leong, Kam W. and Wang,
Shu},
Title = {Peripheral nerve regeneration with sustained release of
poly(phosphoester) microencapsulated nerve growth factor
within nerve guide conduits},
Journal = {Biomaterials},
Volume = {24},
Number = {13},
Pages = {2405 - 2412},
Year = {2003},
url = {http://dx.doi.org/10.1016/S0142-9612(03)00109-1},
Keywords = {Proteins;Implants (surgical);Growth kinetics;Organic
polymers;},
Abstract = {Prolonged delivery of neurotrophic proteins to the target
tissue is valuable in the treatment of various disorders of
the nervous system. We have tested in this study whether
sustained release of nerve growth factor (NGF) within nerve
guide conduits (NGCs), a device used to repair injured
nerves, would augment peripheral nerve regeneration.
NGF-containing polymeric microspheres fabricated from a
biodegradable poly(phosphoester) (PPE) polymer were loaded
into silicone or PPE conduits to provide for prolonged,
site-specific delivery of NGF. The conduits were used to
bridge a 10mm gap in a rat sciatic nerve model. Three months
after implantation, morphological analysis revealed higher
values of fiber diameter, fiber population and fiber density
and lower G-ratio at the distal end of regenerated nerve
cables collected from NGF microsphere-loaded silicone
conduits, as compared with those from control conduits
loaded with either saline alone, BSA microspheres, or NGF
protein without microencapsulation. Beneficial effects on
fiber diameter, G-ratio and fiber density were also observed
in the permeable PPE NGCs. Thus, the results confirm a
long-term promoting effect of exogenous NGF on morphological
regeneration of peripheral nerves. The tissue-engineering
approach reported in this study of incorporation of a
microsphere protein release system into NGCs holds potential
for improved functional recovery in patients whose injured
nerves are reconstructed by entubulation. © 2003
Elsevier Science Ltd. All rights reserved.},
Key = {03177447491}
}
@article{03417666783,
Author = {Liu, Xue-Ming and Yang, Yi-Yan and Leong, Kam
W.},
Title = {Thermally responsive polymeric micellar nanoparticles
self-assembled from cholesteryl end-capped random
poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide):
Synthesis, temperature-sensitivity, and morphologies},
Journal = {Journal of Colloid and Interface Science},
Volume = {266},
Number = {2},
Pages = {295 - 303},
Year = {2003},
url = {http://dx.doi.org/10.1016/S0021-9797(03)00691-X},
Keywords = {Self assembly;Synthesis (chemical);Morphology;Micelles;Transmission
electron microscopy;Thermoanalysis;},
Abstract = {Cholesteryl end-capped thermally responsive amphiphilic
polymers with two different hydrophobic/hydrophilic
chain-length ratios were synthesized from the
hydroxyl-terminated random poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)
and cholesteryl chloroformate. The hydroxyl-terminated
precursor polymers with narrow molecular weight
distributions were synthesized by free-radical
polymerization using 2-hydroxyethanethiol as a
chain-transfer agent. The aqueous solutions of the
cholesteryl end-capped copolymers exhibited reversible phase
transitions at temperatures slightly above human body
temperature, with the lower critical solution temperature
values being 37.7 and 38.2°C, respectively. The critical
micelle concentration values of the two cholesteryl
end-capped polymers were 9 and 25 mg/L, respectively.
Polymeric micellar nanoparticles were prepared from the
amphiphilic polymers using a dialysis method as well as a
direct dissolution method. Transmission electron microscope
studies showed that the micellar nanoparticles existed in
different morphologies, including spherical, star-like, and
cuboid shapes. Pyrene as a model hydrophobic compound could
be readily encapsulated in these polymeric nanoparticles, at
loading levels of 1.0 and 0.8 mg/g for the two cholesteryl
end-capped polymers, respectively. The temperature
sensitivity and unusual morphology of these novel polymeric
nanoparticles would make an interesting drug delivery
system. © 2003 Elsevier Inc. All rights
reserved.},
Key = {03417666783}
}
@article{03177443378,
Author = {Zhao, Zhong and Wang, Jun and Mao, Hai-Quan and Leong, Kam
W.},
Title = {Polyphosphoesters in drug and gene delivery},
Journal = {Advanced Drug Delivery Reviews},
Volume = {55},
Number = {4},
Pages = {483 - 499},
Year = {2003},
url = {http://dx.doi.org/10.1016/S0169-409X(03)00040-1},
Keywords = {Genes;Drug therapy;Biodegradation;Hydrolysis;Biocompatibility;DNA;},
Abstract = {Polymers with repeating phosphoester bonds in the backbone
are structurally versatile, and biodegradable through
hydrolysis, and possibly enzymatic digestion at the
phosphoester linkages under physiological conditions. These
biodegradable polyphosphoesters are appealing for biological
and pharmaceutical applications because of their potential
biocompatibility and similarity to bio-macromolecules such
as nucleic acids. In the first part of this review, we will
focus on one particular structure synthesized by extending
oligomeric lactide prepolymers with ethylphosphate groups.
This amorphous to semi-crystalline polymer is promising in
delivering anti-cancer therapeutics in the form of
microspheres. In the second half, we will discuss the
conjugation of charged groups to the side chain of the
phosphate, constituting one of the few biodegradable
cationic polymers in the field for non-viral gene delivery.
Capable of delivering exogenous genes to a cell nucleus or
providing an extracellular sustained release of DNA, these
cationic polyphosphoesters also serve as a valuable model to
understand the important characteristics that render a
polymer an effective gene carrier. © 2003 Elsevier
Science B.V. All rights reserved.},
Key = {03177443378}
}
@article{03227480633,
Author = {Ying, Lei and Yin, Chao and Zhuo, R.X. and Leong, K.W. and Mao, H.Q. and Kang, E.T. and Neoh, K.G.},
Title = {Immobilization of galactose ligands on acrylic acid
graft-copolymerized poly(ethylene terephthalate) film and
its application to hepatocyte culture},
Journal = {Biomacromolecules},
Volume = {4},
Number = {1},
Pages = {157 - 165},
Year = {2003},
url = {http://dx.doi.org/10.1021/bm025676w},
Keywords = {Graft copolymers;Copolymerization;Surface
treatment;Morphology;Surface roughness;X ray photoelectron
spectroscopy;Atomic force microscopy;},
Abstract = {Surface modification of argon-plasma-pretreated
poly(ethylene terephthalate) (PET) films via UV-induced
graft copolymerization with acrylic acid (AAc) was carried
out. Galactosylated surfaces were then obtained by coupling
a galactose derivative (1-O-(6 prime -aminohexyl)-D-galactopyranoside)
to the AAc graft chains with the aid of a water-soluble
carbodiimide (WSC) and N-hydroxysulfosuccinimide
(sulfo-NHS). The modified PET films were characterized by
X-ray photoelectron spectroscopy (XPS), atomic force
microscopy (AFM), and water contact-angle measurements. The
galactosylated PET films were used as substrates for
hepatocyte culture. The effects of surface carboxyl group
concentration on the extent of galactose ligand
immobilization, the extent of hepatocyte attachment, and the
surface morphology were investigated. The amount of the
galactose ligands immobilized on the PET surface increased
with the AAc polymer graft concentration. AFM images
revealed that the surface roughness of the PET film
increased after graft copolymerization with AAc, but did not
change appreciably with the subsequent immobilization of the
galactose ligands. At the surface carboxyl group
concentration of about 0.56 μmol/cm<sup>2</sup> or
galactose ligand concentration of about 0.51
μmol/cm<sup>2</sup>, the hepatocyte culture on the
galactosylated surface exhibited the optimum concentration
and physiological functions and formed aggregates or
spheroids after just 1 day of culture. The albumin and urea
synthesis functions of these hepatocytes were comparable to
or higher than those of the hepatocytes cultured on the
collagen-modified PET substrates.},
Key = {03227480633}
}
@article{03227480981,
Author = {Fang, Ning and Wang, Jun and Mao, Hai-Quan and Leong, Kam W. and Chan, Vincent},
Title = {BHEM-Chol/DOPE liposome induced perturbation of phospholipid
bilayer},
Journal = {Colloids and Surfaces B: Biointerfaces},
Volume = {29},
Number = {4},
Pages = {233 - 245},
Year = {2003},
url = {http://dx.doi.org/10.1016/S0927-7765(02)00207-2},
Keywords = {Phospholipids;Cell membranes;Lipids;Phase
transitions;Cooling;Enthalpy;Differential scanning
calorimetry;Microscopic examination;},
Abstract = {A new positively charged cholesteryl lipid known as
BHEM-Chol is developed as a membrane perturbant. It has been
shown that this cationic liposome effectively fuses with
cell membrane. In this study, the interaction between
BHEM-Chol/DOPE liposome and dipalmitoylphosphocholine (DPPC)
bilayer is investigated with cross-polarization microscopy,
differential scanning calorimetry (DSC) and cooperative unit
analysis in order to aid the physical understanding in the
cationic liposome-biological membrane interaction. The
presence of BHEM-Chol/DOPE liposome in DPPC/water mixture
leads to the formation of larger multilamellar vesicles
(MLV) and also induces fusions of pre-assembled MLV. The
pre-transition peak of DPPC bilayer is abolished under the
influence BHEM-Chol/DOPE liposome. When the mole fraction of
BHEM-Chol/DOPE liposome is increased from 0 to 0.7, the
calorimetric enthalpy of DPPC bilayer is reduced by 63%.
Simultaneously, the phase transition temperature of DPPC
bilayer is shifted to lower value and is accompanied by the
reduction of cooperative unit. The thermotropic property of
DPPC bilayer during sample cooling is also affected by this
new liposome system. In addition, the interaction between
DPPC bilayer and a commercial DC-Chol/DOPE liposome is used
as a reference. Most important, BHEM-Chol provides the major
driving force for membrane perturbation as shown by the 38%
reduction in calorimetric enthalpy in aqueous DPPC/BHEM-Chol
mixture. Cell culture media further modulates the structural
properties of the aqueous mixture. In addition, in vitro
transfection studies of COS-7 cells mediated by both
BHEM-Chol/DOPE and DC-Chol/DOPE liposomes are presented and
provide a qualitative correlation with our biophysical
measurements. © 2002 Elsevier Science B.V. All rights
reserved.},
Key = {03227480981}
}
@article{03397650351,
Author = {Wen, Jie and Kim, Gloria J.A. and Leong, Kam
W.},
Title = {Poly(D,Llactide-co-ethyl ethylene phosphate)s as new drug
carriers},
Journal = {Journal of Controlled Release},
Volume = {92},
Number = {1-2},
Pages = {39 - 48},
Year = {2003},
url = {http://dx.doi.org/10.1016/S0168-3659(03)00294-3},
Keywords = {Phosphates;Ethylene;Biodegradation;Drug therapy;Ring opening
polymerization;},
Abstract = {Many biodegradable polymers have been developed for
controlled drug delivery. The plethora of drug therapies and
types of drugs demand different formulations, fabrications
conditions and release kinetics. No one single polymer can
satisfy all the requirements. To extend the properties of
poly(D,L-lactide) (PLA), we synthesized copolymers of PLA
and poly(ethylethylene phosphate) (PEEP) by ring-opening
polymerization using Al(O<sup>i</sup>pr)<sub>3</sub> as the
initiator. The copolymers were structurally characterized by
IR and <sup>1</sup>H NMR. DSC data confirmed the formation
of random microphase structure in all the copolymers, and
showed a decrease of T<sub>g</sub> from 43.2 to -22.6°C
when the molar content of ethylethylene phosphate (EEP)
increased from 5 to 40%. The hydrophilicity of the
copolymers increased with EEP content. In contrast to the
degradation behavior of PLA, disc samples made of PLAEEP90
showed a linear weight loss profile in PBS (pH 7.4) at
37°C. BSA microspheres using PLAEEP90 were prepared by
double-emulsion method, yielding a loading level of 4.3% and
a loading efficiency of 75%. The BSA release profile
consisted of an initial burst (9%) on the first day,
followed by a daily 4% release for the following 40 days,
resulting in 91% of the BSA release in a near linear manner.
The released BSA remained intact according to SDS-PAGE data.
Cytotoxicity and histopathology studies showed low toxicity
in HeLa cells and good tissue biocompatibility in mouse
brain, respectively. PLAEEP is a promising biodegradable
polymer for controlled drug delivery. © 2003 Elsevier
B.V. All rights reserved.},
Key = {03397650351}
}
@article{7645332,
Author = {Chao Yin and Kin Liao and Hai-Quan Mao and Leong, K.W. and Ren-Xi Zhuo and Chan, V.},
Title = {Adhesion contact dynamics of HepG2 cells on
galactose-immobilized substrates},
Journal = {Biomaterials (UK)},
Volume = {24},
Number = {5},
Pages = {837 - 50},
Year = {2003},
url = {http://dx.doi.org/10.1016/S0142-9612(02)00416-7},
Keywords = {biological techniques;biomedical measurement;cellular
biophysics;liver;molecular biophysics;optical
microscopy;proteins;substrates;},
Abstract = {The specific recognition between asialoglycoprotein receptor
and galactose ligand at cell-substrate interfaces has been
shown to mediate hepatocyte adhesion and maintain liver
specific functions of hepatocytes. Conventionally, the
success of hepatocyte attachment oil engineered tissue
scaffold is inferred from the degree of two-dimensional cell
spreading that is measured by transmitted light microscopy.
However, the actual contact mechanics and adhesion strength
of hepatocytes during two-dimensional cell spreading has not
been elucidated due to lack of biophysical probe. In this
stud, a novel biophysical technique known as confocal
reflectance interference contrast microscopy (C-RICM) in
conjunction with phase contrast microscopy is utilized to
probe the adhesion dynamics, contact mechanics and
two-dimensional spreading kinetics of HepG2 cells on
galactose immobilized and collagen gel coated substrates.
C-RICM demonstrates that HepG2 cells form strong adhesion
contacts with both galactose-immobilized Surfaces and
collagen gel coated substrates. Moreover, HepG2 cells
maintain their compact shapes in the presence of
asialoglycoprotein receptor-mediated recognition while they
become exceedingly spread under integrin-mediated adhesion
on collagen gel coated substrate. The initial rate of
adhesion contact formation and the steady-state adhesion
energy of HepG2 cell population are highest oil substrate
conjugated with galactose ligand via a longer spacer. The
adhesion dynamics and final adhesion energy of HepG2 cells
depends both on the type of ligand-receptor interaction and
the length of spacer between the ligand and substrate. Most
importantly, new biophysical insights into the initial
hepatocyte attachment that are critical for hepatocyte
Culture are provided through the decomposition of
two-dimensional spreading and adhesion contact formation on
bio-functional substrates},
Key = {7645332}
}
@article{Article,
Author = {Li, J. and Ni, X. P. and Leong, K. W.},
Title = {Injectable drug-delivery systems based on supramolecular
hydrogels formed by poly(ethylene oxide) and
alpha-cyclodextrin},
Journal = {Journal of Biomedical Materials Research Part
A},
Volume = {65A},
Number = {2},
Pages = {196-202},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Salem, A. K. and Searson, P. C. and Leong, K.
W.},
Title = {Multifunctional nanorods for gene delivery},
Journal = {Nature Materials},
Volume = {2},
Number = {10},
Pages = {668-671},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Du, X. Y. and Yang, Y. S. and Le Visage and C. and Chen, H. H. and DeJong, R. and Qiu, B. S. and Wang, D. M. and Leong, K.
W. and Hamper, U. M. and Yang, X. M.},
Title = {In vivo US monitoring of catheter-based vascular delivery of
gene microspheres in pigs: Feasibility},
Journal = {Radiology},
Volume = {228},
Number = {2},
Pages = {555-559},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Chew, J. L. and Wolfowicz, C. B. and Mao, H. Q. and Leong,
K. W. and Chua, K. Y.},
Title = {Chitosan nanoparticles containing plasmid DNA encoding house
dust mite allergen, Der p 1 for oral vaccination in
mice},
Journal = {Vaccine},
Volume = {21},
Number = {21-22},
Pages = {2720-2729},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Lu, H. F. and Lim, W. S. and Wang, J. and Tang, Z. Q. and Zhang, P. C. and Leong, K. W. and Chia, S. M. and Yu, H. and Mao, H. Q.},
Title = {Galactosylated PVDF membrane promotes hepatocyte attachment
and functional maintenance},
Journal = {Biomaterials},
Volume = {24},
Number = {27},
Pages = {4893-4903},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Ying, L. and Yin, C. and Zhuo, R. X. and Leong, K. W. and Mao, H. Q. and Kang, E. T. and Neoh, K. G.},
Title = {Immobilization of galactose ligands on acrylic acid
graft-copolymerized poly(ethylene terephthalate) film and
its application to hepatocyte culture},
Journal = {Biomacromolecules},
Volume = {4},
Number = {1},
Pages = {157-165},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Fang, N. and Wang, J. and Mao, H. Q. and Leong, K. W. and Chan, V.},
Title = {BHEM-Chol/DOPE liposome induced perturbation of phospholipid
bilayer},
Journal = {Colloids and Surfaces B-Biointerfaces},
Volume = {29},
Number = {4},
Pages = {233-245},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Zhao, Z. and Wang, J. and Mao, H. Q. and Leong, K.
W.},
Title = {Polyphosphoesters in drug and gene delivery},
Journal = {Advanced Drug Delivery Reviews},
Volume = {55},
Number = {4},
Pages = {483-499},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Shi, L. and Tang, G. P. and Gao, S. J. and Ma, Y. X. and Liu, B. H. and Li, Y. and Zeng, J. M. and Ng, Y. K. and Leong, K. W. and Wang, S.},
Title = {Repeated intrathecal administration of plasmid DNA complexed
with polyethylene glycol-grafted polyethylenimine led to
prolonged transgene expression in the spinal
cord},
Journal = {Gene Therapy},
Volume = {10},
Number = {14},
Pages = {1179-1188},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Li, X. and Li, J. and Leong, K. W.},
Title = {Preparation and characterization of inclusion complexes of
biodegradable amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene
oxide) triblock copolymers with cyclodextrins},
Journal = {Macromolecules},
Volume = {36},
Number = {4},
Pages = {1209-1214},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Li, J. and Ni, X. P. and Leong, K.},
Title = {Block-selected molecular recognition and formation of
polypseudorotaxanes between poly(propylene oxide)-poly
(ethylene oxide)poly(propylene oxide) triblock copolymers
and alpha-cyclodextrin},
Journal = {Angewandte Chemie-International Edition},
Volume = {42},
Number = {1},
Pages = {69-72},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Wang, J. and Huang, S. W. and Zhang, P. C. and Mao, H. Q. and Leong, K. W.},
Title = {Effect of side-chain structures on gene transfer efficiency
of biodegradable cationic polyphosphoesters},
Journal = {International Journal of Pharmaceutics},
Volume = {265},
Number = {1-2},
Pages = {75-84},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Yin, C. and Ying, L. and Zhang, P. C. and Zhuo, R. X. and Kang, E. T. and Leong, K. W. and Mao, H.
Q.},
Title = {High density of immobilized galactose ligand enhances
hepatocyte attachment and function},
Journal = {Journal of Biomedical Materials Research Part
A},
Volume = {67A},
Number = {4},
Pages = {1093-1104},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Sun, T. and Chan, M. L. H. and Zhou, Y. and Xu, X. and Zhang, J. and Lao, X. J. and Wang, X. W. and Quek, C. H. and Chen, J. P. and Leong, K. W. and Yu, H.},
Title = {Use of ultrathin shell microcapsules of hepatocytes in
bioartificial liver-assist device},
Journal = {Tissue Engineering},
Volume = {9},
Pages = {S65-S75},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Li, J. and Ni, X. P. and Zhou, Z. H. and Leong, K.
W.},
Title = {Preparation and characterization of polypseudorotaxanes
based on block-selected inclusion complexation between
poly(propylene oxide)-poly(ethylene oxide)-poly(propylene
oxide) triblock copolymers and alpha-cyclodextrin},
Journal = {Journal of the American Chemical Society},
Volume = {125},
Number = {7},
Pages = {1788-1795},
Year = {2003},
Key = {Article}
}
@article{Article,
Author = {Yin, C. and Liao, K. and Mao, H. Q. and Leong, K. W. and Zhuo, R. X. and Chan, V.},
Title = {Adhesion contact dynamics of HepG2 cells on
galactose-immobilized substrates},
Journal = {Biomaterials},
Volume = {24},
Number = {5},
Pages = {837-850},
Year = {2003},
Key = {Article}
}
@article{7522916,
Author = {Xiangying Du and Yuesong Yang and Le Visage and C. and Chen,
H.H. and DeJong, R. and Bensheng Qiu and Danming Wang and Leong, K.W. and Hamper, U.M. and Xiaoming
Yang},
Title = {Microsphere as a contrast agent/gene vector in ultrasound
imaging-based vascular gene delivery},
Journal = {2002 IEEE International Symposium on Biomedical Imaging
(Cat. No.02EX608)},
Pages = {989 - 92},
Address = {Washington, DC, USA},
Year = {2002},
url = {http://dx.doi.org/10.1109/ISBI.2002.1029429},
Keywords = {biochemistry;biomedical ultrasonics;blood
vessels;cardiovascular system;catheters;fluorescence;genetics;patient
treatment;proteins;},
Abstract = {The purpose of this study was to test the feasibility of
using a novel biodegradable microsphere as a contrast
agent/gene vector in ultrasound imaging-based vascular gene
delivery. We first encapsulated green fluorescent protein
(GFP) gene into the microspheres and validated the echogenic
property of GFP-plasmid/microspheres with intramuscular
injection. Then, the GFP-plasmid/microspheres were
transferred into the arteries of pigs via a catheter-based
delivery procedure under ultrasound imaging. A strong
echogenic signal reflected from the microspheres indicated
the destination of genes delivered, whereas functional gene
expression was confirmed by immunohistochemical examination.
Microspheres can be feasible contrast agents/gene vectors in
ultrasound imaging-based vascular gene delivery in
vivo},
Key = {7522916}
}
@article{01546795996,
Author = {Chia, S.M. and Wan, A.C.A. and Quek, C.H. and Mao, H.Q. and Xu, X. and Shen, L. and Ng, M.L. and Leong, K.W. and Yu,
H.},
Title = {Multi-layered microcapsules for cell encapsulation},
Journal = {Biomaterials},
Volume = {23},
Number = {3},
Pages = {849 - 856},
Year = {2002},
url = {http://dx.doi.org/10.1016/S0142-9612(01)00191-0},
Keywords = {Cells;Encapsulation;Collagen;Organic acids;Monolayers;Sol-gels;Tissue;},
Abstract = {Mechanical stability, complete encapsulation, selective
permeability, and suitable extra-cellular microenvironment,
are the major considerations in designing microcapsules for
cell encapsulation. We have developed four types of
multi-layered microcapsules that allow selective
optimization of these parameters. Primary hepatocytes were
used as model cells to test these different microcapsule
configurations. Type-I microcapsules with an average
diameter of 400 μm were formed by complexing modified
collagen with a ter-polymer shell of 2-hydroxyethyl
methylacrylate (HEMA), methacrylic acid (MAA) and methyl
methacrylate (MMA), resulting in a capsule thickness of 2-5
μm. Cells in these microcapsules exhibited improved
cellular functions over those cultured on collagen
monolayers. Type-II microcapsules were formed by
encapsulating the Type-I microcapsules in another 2-5 μm
ter-polymer shell and a [similar to] 5 μm collagen layer
between the two ter-polymer shells to ensure complete cell
encapsulation. Type-III microcapsules comprised of a
macro-porous exoskeleton with materials such as alumina
sol-gel coated on the Type-I microcapsules. Nano-indendation
assay indicated an improved mechanical stability over the
Type-I microcapsules. Type-IV microcapsules were created by
encapsulating Type-III microcapsules in another 2-5 μm
ter-polymer shell, with the aim of imparting a negatively
charged smooth surface to minimize plasma protein absorption
and ensure complete cell encapsulation. The permeability for
nutrient exchange, cellular functions in terms of urea
production and mechanical stability of the microcapsules
were characterized. The advantages and limitations of these
microcapsules for tissue engineering are discussed. ©
2001 Elsevier Science Ltd. All rights reserved.},
Key = {01546795996}
}
@article{05219116798,
Author = {Chia, Ser-Mien and Zhou, Yi and Sun, Tao and Mao, Hai-Quan and Leong, Kam W. and Chen, Jia-Ping and Yu,
Hanry},
Title = {Issues and technologies leading to a new bio-artificial
liver with microencapsulated hepatocytes},
Journal = {Third Smith and Nephew International Symposium - Translating
Tissue Engineering into Products},
Pages = {71 -},
Address = {Atlanta, GA, United States},
Year = {2002},
Keywords = {Cells;Bioreactors;Immunology;Mass transfer;Biochemistry;Collagen;Cell
culture;Biomaterials;Terpolymers;Electrohydrodynamics;},
Abstract = {The efforts being made to address a number of relevant
issues and to develop the means for a new bio-artificial
liver based on the microcapsules are discussed. The four
classes of configurable microcapsules with controllable
mechanical stabilities, and one class of the fragile
microcapsules have been successfully applied to culture. To
scale up the production of encapsulating hepatocytes in such
ultra-thin microcapsules, the relationship between the
physical, and chemical parameters of the biomaterials, and
the microcapsules. An electro-hydrodynamic method, and a
device are also developed of forming the microcapsules with
well-controlled diameters, and shell thickness.},
Key = {05219116798}
}
@article{7516448,
Author = {Chen, H.H. and Le Visage and C. and Bensheng Qiu and Xiangying
Du and Ouwerkerk, R. and Leong, K.W. and Xiaoming
Yang},
Title = {Novel method for imaging biodegradable polymeric
microparticles using MRI: application toward monitoring drug
delivery},
Journal = {2002 IEEE International Symposium on Biomedical Imaging
(Cat. No.02EX608)},
Pages = {145 - 8},
Address = {Washington, DC, USA},
Year = {2002},
url = {http://dx.doi.org/10.1109/ISBI.2002.1029214},
Keywords = {biological organs;biomedical materials;biomedical
MRI;cancer;drug delivery systems;patient
monitoring;},
Abstract = {We have developed a novel, non-invasive method to monitor
intravesical drug delivery to the bladder using MRI by
encapsulating Gd-DTPA into biodegradable polymeric
microparticles. In in vitro experiments, Gd-DTPA-loaded
particles could be differentiated from blank particles and
water. Images from in vivo experiments demonstrated that
particle distribution in the bladder could be assessed and
that signal intensity appeared to correspond with particle
population. The microparticles were adherent to the
urothelium and were detectable by MRI for at least 4 days
after the initial instillation due to their
muco-adhesiveness and stability. This non-invasive method
enables the evaluation of local particle distribution in
vivo, thereby enhancing the value of particle-based drug
delivery systems},
Key = {7516448}
}
@article{02266989173,
Author = {Xu, Xiaoyun and Yu, Hanry and Gao, Shujun and Mao, Hai-Quan and Leong, Kam W. and Wang, Shu},
Title = {Polyphosphoester microspheres for sustained release of
biologically active nerve growth factor},
Journal = {Biomaterials},
Volume = {23},
Number = {17},
Pages = {3765 - 3772},
Year = {2002},
url = {http://dx.doi.org/10.1016/S0142-9612(02)00116-3},
Keywords = {Esters;Proteins;Polymers;Implants (surgical);Biodegradation;Antibodies;Neurology;Evaporation;Extraction;Assays;},
Abstract = {Controlled delivery of neurotrophic proteins to a target
tissue by biodegradable polymer microspheres has been
explored widely for its potential applications in the
treatment of various disorders in the nervous system. We
investigated in this study the potential of polyphosphoester
microspheres as carriers for the sustained release of nerve
growth factor (NGF), a water-soluble neurotrophic protein.
Two polyphosphoesters (PPEs), P(BHET-EOP/TC) and
P(DAPG-EOP), as well as poly(lactide/glycolic acid) (PLGA),
were used to fabricate microspheres by a W/O/W emulsion and
solvent evaporation/extraction method. With bovine serum
albumin as a model protein to optimize processing
parameters, P(DAPG-EOP) microspheres exhibited a lower burst
effect but similar protein entrapment levels and
efficiencies when compared with those made of PLGA.
Bioactive NGF could be released for at least 10 weeks from
the P(DAPG-EOP) microspheres, as confirmed by a neurite
outgrowth assay of the PC12 cells. These NGF containing
microspheres were incorporated into the nerve guide conduits
that were implanted to bridge a 10mm gap in a rat sciatic
nerve model. Two weeks after implantation, immunostaining
with an antibody against the neurofilament protein confirmed
the presence of axons at the distal end of regenerated
cables within the NGF microsphere-loaded conduits. These
results demonstrated the feasibility of using biodegradable
PPEs for microencapsulation of NGF and provided a basis for
future therapeutic application of the microspheres. ©
2002 Elsevier Science Ltd. All rights reserved.},
Key = {02266989173}
}
@article{Article,
Author = {Du, X. Y. and Yang, Y. S. and Le Visage and C. and Chen, H. H. and DeJong, R. and Wang, D. M. and Leong, K. W. and Hamper,
U. M. and Yang, X. M.},
Title = {In vivo ultrasound imaging of catheter-based vascular
gene/microsphere delivery},
Journal = {Circulation},
Volume = {106},
Number = {19},
Pages = {M-M},
Year = {2002},
Key = {Article}
}
@article{8701823,
Author = {Chen, H.H. and Le Visage and C. and Qiu, B. and Du, X. and Ouwerkerk, R. and Leong, K.W. and Yang, X.},
Title = {Novel method for imaging biodegradable polymeric
microparticles using MRI: application toward monitoring drug
delivery},
Journal = {2002 IEEE International Symposium on Biomedical
Imaging},
Pages = {4 pp. -},
Address = {Washington, DC, USA},
Year = {2002},
Keywords = {biological organs;biomedical MRI;cancer;drugs;organic
compounds;patient monitoring;tumours;},
Abstract = {We have developed a novel, non-invasive method to monitor
intravesical drug delivery to the bladder using MRI by
encapsulating Gd-DTPA into biodegradable polymeric
microparticles. In in vitro experiments, Gd-DTPA-loaded
particles could be differentiated from blank particles and
water. Images from in vivo experiments demonstrated that
particle distribution in the bladder could be assessed and
that signal intensity appeared to correspond with particle
population. The microparticles were adherent to the
urothelium and were detectable by MRI for at least 4 days
after the initial instillation due to their
muco-adhesiveness and stability. This non-invasive method
enables the evaluation of local particle distribution in
vivo, thereby enhancing the value of particle-based drug
delivery systems},
Key = {8701823}
}
@article{Article,
Author = {Chia, S. M. and Wan, A. C. A. and Quek, C. H. and Mao, H. Q. and Xu, X. and Shen, L. and Ng, M. L. and Leong, K. W. and Yu, H.},
Title = {Multi-layered microcapsules for cell encapsulation},
Journal = {Biomaterials},
Volume = {23},
Number = {3},
Pages = {849-856},
Year = {2002},
Key = {Article}
}
@article{Article,
Author = {Wang, J. and Zhang, P. C. and Lu, H. F. and Ma, N. and Wang,
S. and Mao, H. Q. and Leong, K. W.},
Title = {New polyphosphoramidate with a spermidine side chain as a
gene carrier},
Journal = {Journal of Controlled Release},
Volume = {83},
Number = {1},
Pages = {157-168},
Year = {2002},
Key = {Article}
}
@article{Article,
Author = {Chew, J. L. and Fu, T. Q. H. and Mao, H. Q. and Leong, K. W. and Chua, K. Y.},
Title = {Oral administration of major house dust mite allergen genes
complexed with chitosan elicits protective Th1-skewed
immunity in mice},
Journal = {Allergy},
Volume = {57},
Pages = {64-64},
Year = {2002},
Key = {Article}
}
@article{Article,
Author = {Fang, N. and Chan, V. and Wan, K. T. and Mao, H. Q. and Leong, K. W.},
Title = {Colloidal adhesion of phospholipid vesicles: high-resolution
reflection interference contrast microscopy and
theory},
Journal = {Colloids and Surfaces B-Biointerfaces},
Volume = {25},
Number = {4},
Pages = {347-362},
Year = {2002},
Key = {Article}
}
@article{Article,
Author = {Xu, X. Y. and Yu, H. and Gao, S. J. and Mao, H. Q. and Leong, K. W. and Wang, S.},
Title = {Polyphosphoester microspheres for sustained release of
biologically active nerve growth factor},
Journal = {Biomaterials},
Volume = {23},
Number = {17},
Pages = {3765-3772},
Year = {2002},
Key = {Article}
}
@article{Article,
Author = {Wang, J. and Zhang, P. C. and Mao, H. Q. and Leong, K.
W.},
Title = {Enhanced gene expression in mouse muscle by sustained
release of plasmid DNA using PPE-EA as a
carrier},
Journal = {Gene Therapy},
Volume = {9},
Number = {18},
Pages = {1254-1261},
Year = {2002},
Key = {Article}
}
@article{Article,
Author = {Kumar, M. and Behera, A. K. and Lockey, R. F. and Zhang, J. and Bhullar, G. and De La Cruz and C. P. and Chen, L. C. and Leong, K. W. and Huang, S. K. and Mohapatra, S.
S.},
Title = {Intranasal gene transfer by chitosan-DNA nanospheres
protects BALB/c mice against acute respiratory syncytial
virus infection},
Journal = {Human Gene Therapy},
Volume = {13},
Number = {12},
Pages = {1415-1425},
Year = {2002},
Key = {Article}
}
@article{Article,
Author = {Peng, B. G. and Liu, S. Q. and Kuang, M. and He, Q. and Totsuka, S. and Huang, L. and Huang, J. F. and Lu, M. D. and Liang, L. J. and Leong, K. W. and Ohno, T.},
Title = {Autologous fixed tumor vaccine: A formulation with
cytokine-microparticles for protective immunity against
recurrence of human hepatocellular carcinoma},
Journal = {Japanese Journal of Cancer Research},
Volume = {93},
Number = {4},
Pages = {363-368},
Year = {2002},
Key = {Article}
}
@article{7380435,
Author = {Ning Fang and Chan, V. and Kai-Tak Wan and Hai-Quan Mao and Leong, K.W.},
Title = {Colloidal adhesion of phospholipid vesicles: high-resolution
reflection interference contrast microscopy and
theory},
Journal = {Colloids Surf. B, Biointerfaces (Netherlands)},
Volume = {25},
Number = {4},
Pages = {347 - 62},
Year = {2002},
url = {http://dx.doi.org/10.1016/S0927-7765(01)00336-8},
Keywords = {adhesion;biological techniques;biomembranes;colloids;image
resolution;optical microscopy;organic compounds;osmosis;pH;},
Abstract = {High-resolution reflection interference contrast microscopy
(HR-RICM) was developed for probing the deformation and
adhesion of phospholipid vesicles induced by colloidal
forces on solid surfaces. The new technique raised the upper
limit of the measured membrane-substrate separation from 1
to 4.5 μm and improved the spatial resolution of the
heterogeneous contact zones. It was applied to elucidate the
effects of wall thickness, pH and osmotic stress on the
non-specific adhesion of giant unilamellar vesicles (ULV)
and multilamellar vesicles (MLV) on fused silica substrates.
By simultaneous cross-polarization light microscopy and
HR-RICM measurements, it was observed that ULV with the wall
thickness of a single bilayer would be significantly
deformed in its equilibrium state on the substrate as the
dimension of its adhesive-cohesive zone was 29% higher than
the theoretical value of a rigid sphere with the same
diameter. Besides, electrostatic interaction was shown as a
significant driving force for vesicle adhesions since the
reduction in pH significantly increased the degree of
deformation of adhering ULV and heterogeneity of the
adhesion discs. The degree of MLV deformation on the solid
surfaces was significantly less than that of ULV. When the
wall thickness of vesicle increased, the dimension of
contact zone was reduced dramatically due to the increase of
membrane bending modulus. Most important, the adhesion
strength of colloidal adhesion approached that of specific
adhesion. Finally, the increase of osmotic stress led to the
collapse of adhering vesicles on the non-deformable
substrate and raised the area of adhesive contact zone. To
interpret these results better, the equilibrium deformation
of adhering vesicle was modeled as a truncated sphere and
the adhesion energy was calculated with a new
theory},
Key = {7380435}
}
@article{01456715473,
Author = {Wang, J. and Mao, H.-Q. and Leong, K.W.},
Title = {A novel biodegradable gene carrier based on polyphosphoester
[19]},
Journal = {Journal of the American Chemical Society},
Volume = {123},
Number = {38},
Pages = {9480 - 9481},
Year = {2001},
url = {http://dx.doi.org/10.1021/ja016062m},
Key = {01456715473}
}
@article{Article,
Author = {Wan, A. C. A. and Mao, H. Q. and Wang, S. and Leong, K. W. and Ong, Lkll and Yu, H.},
Title = {Fabrication of poly(phosphoester) nerve guides by immersion
precipitation and the control of porosity},
Journal = {Biomaterials},
Volume = {22},
Number = {10},
Pages = {1147-1156},
Year = {2001},
Key = {Article}
}
@article{02046834590,
Author = {Li, Jun and Li, Xu and Toh, Kee Chua and Ni, Xiping and Zhou, Zhihan and Leong, Kam W.},
Title = {Inclusion complexation and formation of polypseudorotaxanes
between poly[(ethylene oxide)-ran-(propylene oxide)] and
cyclodextrins},
Journal = {Macromolecules},
Volume = {34},
Number = {26},
Pages = {8829 - 8831},
Year = {2001},
url = {http://dx.doi.org/10.1021/ma011129b},
Keywords = {Complexation;Inclusions;Molecular weight;Temperature;Solubility;Composition;Solutions;Filtration;Centrifugation;Water;X
ray diffraction analysis;},
Abstract = {P(EO-r-PO) copolymers with PO units of 20 mol% were studied
and shown to form inclusion complexes with α-CD and
γ-CD to give polypseudorotaxanes in high yields. It
was found that both polypseudorotaxanes are crystalline and
assume a channel-type structure. The results contradict the
conventional wisdom that α-CD would not be large
enough to thread over a PO unit.},
Key = {02046834590}
}
@article{01506763107,
Author = {Li, J. and Li, X. and Zhou, Z. and Ni, X. and Leong,
K.W.},
Title = {Formation of supramolecular hydrogels induced by inclusion
complexation between pluronics and α-cyclodextrin
[2]},
Journal = {Macromolecules},
Volume = {34},
Number = {21},
Pages = {7236 - 7237},
Year = {2001},
url = {http://dx.doi.org/10.1021/ma010742s},
Key = {01506763107}
}
@article{6996653,
Author = {Ramakrishna, S. and Mayer, J. and Wintermantel, E. and Leong, K.W.},
Title = {Biomedical applications of polymer-composite materials: A
review},
Journal = {Compos. Sci. Technol. (UK)},
Volume = {61},
Number = {9},
Pages = {1189 - 224},
Year = {2001},
url = {http://dx.doi.org/10.1016/S0266-3538(00)00241-4},
Keywords = {composite materials;elastic moduli;polymers;prosthetics;reviews;},
Abstract = {An overview of various biomedical applications of
polymer-composite materials reported in the literature over
the last 30 years is presented in this paper. For the
benefit of the readers, general information regarding
structure and function of tissues, types and purpose of
implants/medical devices, and various other materials used,
are also briefly presented. Different types of polymer
composite that are already in use or are investigated for
various biomedical applications are presented. Specific
advantages of using polymer-composite biomaterials in
selected applications are also highlighted. The paper also
examines the critical issues and scientific challenges that
require further research and development of polymer
composite materials for their increased acceptance in the
biomedical industry},
Key = {6996653}
}
@article{Article,
Author = {Hanes, J. and Sills, A. and Zhao, Z. and Suh, K. W. and Tyler, B. and DiMeco, F. and Brat, D. J. and Choti, M. A. and Leong, K. W. and Pardoll, D. M. and Brem,
H.},
Title = {Controlled local delivery of interleukin-2 by biodegradable
polymers protects animals from experimental brain tumors and
liver tumors},
Journal = {Pharmaceutical Research},
Volume = {18},
Number = {7},
Pages = {899-906},
Year = {2001},
Key = {Article}
}
@article{02487241806,
Author = {Chan, Vincent and Mao, Hai-Quan and Leong, Kam
W.},
Title = {Chitosan-induced perturbation of dipalmitoyl-sn-glycero-3-phosphocholine
membrane bilayer},
Journal = {Langmuir},
Volume = {17},
Number = {12},
Pages = {3749 - 3756},
Year = {2001},
url = {http://dx.doi.org/10.1021/la001754u},
Keywords = {Bilaminate membranes;Mixing;Hydration;Mixtures;Enthalpy;Phase
transitions;Thermotropic liquid crystals;Molecular
dynamics;Hydrophobicity;Genes;Assays;Raman
scattering;Differential scanning calorimetry;Fourier
transforms;},
Abstract = {Recently, chitosan, a positively charged polysaccharide in
slightly acidic condition, has been used as a membrane
perturbant in a novel gene delivery assay. In this study,
the fundamental interactions between chitosan and DPPC
membrane bilayers were investigated with cross-polarization
microscopy, differential scanning calorimetry and Fourier
transform (FT) Raman spectroscopy. The cross-polarized
images showed that chitosan induced fusions of multilamellar
vesicles. It was determined that the mixing of chitosan with
dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and
subsequent hydration of the mixture at 60 °C
significantly suppressed the enthalpy of the gel-liquid
crystalline transition in a concentration-dependent manner.
Chitosan also affected the thermotropic behavior of DPPC
bilayer during the cooling cycle. However, chitosan addition
to DPPC had no effect on the main phase transition
temperature (T<sub>m</sub>) of DPPC bilayers. When DPPC and
chitosan were mixed in chloroform before hydration, the
initial rate of enthalpy reduction against chitosan
concentration was significantly increased. Furthermore, the
dependence of the cooperative unit of the DPPCs main
transition on the chitosan mole fraction showed that
chitosan tuned the intermolecular interactions between
neighboring lipid molecules. FT-Raman spectroscopy provided
solid evidence that the attractive interchain and
intermolecular forces of the hydrophobic core (acyl chains)
in the DPPC bilayer were significantly reduced by the
chitosan-membrane interactions. The addition of chitosan
also reduced the order in the two-dimensional packing of the
acyl chains and increased the fluidity of the DPPC bilayer.
This study provided new insights into the physicochemical
interactions between model membrane and chitosan that might
aid the development of a novel membrane perturbant for gene
delivery.},
Key = {02487241806}
}
@article{Article,
Author = {Wang, S. and Ma, N. and Gao, S. J. and Yu, H. and Leong, K.
W.},
Title = {Transgene expression in the brain stem effected by
intramuscular injection of polyethylenimine/DNA
complexes},
Journal = {Molecular Therapy},
Volume = {3},
Number = {5},
Pages = {658-664},
Year = {2001},
Key = {Article}
}
@article{Article,
Author = {Li, J. and Li, X. and Zhou, Z. H. and Ni, X. P. and Leong,
K. W.},
Title = {Formation of supramolecular hydrogels induced by inclusion
complexation between pluronics and alpha-cyclodextrin},
Journal = {Macromolecules},
Volume = {34},
Number = {21},
Pages = {7236-7237},
Year = {2001},
Key = {Article}
}
@article{Article,
Author = {Ramakrishna, S. and Mayer, J. and Wintermantel, E. and Leong, K. W.},
Title = {Biomedical applications of polymer-composite materials: a
review},
Journal = {Composites Science and Technology},
Volume = {61},
Number = {9},
Pages = {1189-1224},
Year = {2001},
Key = {Article}
}
@article{Article,
Author = {Chan, V. and Mao, H. Q. and Leong, K. W.},
Title = {Chitosan-induced perturbation of dipalmitoyl-sn-glycero-3-phosphocholine
membrane bilayer},
Journal = {Langmuir},
Volume = {17},
Number = {12},
Pages = {3749-3756},
Year = {2001},
Key = {Article}
}
@article{Article,
Author = {Mao, H. Q. and Roy, K. and Troung-Le, V. L. and Janes, K. A. and Lin, K. Y. and Wang, Y. and August, J. T. and Leong, K.
W.},
Title = {Chitosan-DNA nanoparticles as gene carriers: synthesis,
characterization and transfection efficiency},
Journal = {Journal of Controlled Release},
Volume = {70},
Number = {3},
Pages = {399-421},
Year = {2001},
Key = {Article}
}
@article{Article,
Author = {Wang, S. and Wan, A. C. A. and Xu, X. Y. and Gao, S. J. and Mao, H. Q. and Leong, K. W. and Yu, H.},
Title = {A new nerve guide conduit material composed of a
biodegradable poly(phosphoester)},
Journal = {Biomaterials},
Volume = {22},
Number = {10},
Pages = {1157-1169},
Year = {2001},
Key = {Article}
}
@article{Article,
Author = {Wang, J. and Mao, H. Q. and Leong, K. W.},
Title = {A novel biodegradable gene carrier based on
polyphosphoester},
Journal = {Journal of the American Chemical Society},
Volume = {123},
Number = {38},
Pages = {9480-9481},
Year = {2001},
Key = {Article}
}
@article{Article,
Author = {Fang, N. and Chan, V. and Mao, H. Q. and Leong, K.
W.},
Title = {Interactions of phospholipid bilayer with chitosan: effect
of molecular weight and pH},
Journal = {Biomacromolecules},
Volume = {2},
Number = {4},
Pages = {1161-1168},
Year = {2001},
Key = {Article}
}
@article{Article,
Author = {Li, J. and Li, X. and Toh, K. C. and Ni, X. P. and Zhou, Z.
H. and Leong, K. W.},
Title = {Inclusion complexation and formation of polypseudorotaxanes
between poly[(ethylene oxide)-ran-(propylene oxide)] and
cyclodextrins},
Journal = {Macromolecules},
Volume = {34},
Number = {26},
Pages = {8829-8831},
Year = {2001},
Key = {Article}
}
@article{Article,
Author = {Georgantas, R. W. and Leong, K. W. and August, J.
T.},
Title = {Antigen-specific induction of peripheral T cell tolerance in
vivo by codelivery of DNA vectors encoding antigen and Fas
ligand},
Journal = {Human Gene Therapy},
Volume = {11},
Number = {6},
Pages = {851-858},
Year = {2000},
Key = {Article}
}
@article{Article,
Author = {Chia, S. M. and Leong, K. W. and Li, J. and Xu, X. and Zeng,
K. Y. and Er, P. N. and Gao, S. J. and Yu,
H.},
Title = {Hepatocyte encapsulation for enhanced cellular
functions},
Journal = {Tissue Engineering},
Volume = {6},
Number = {5},
Pages = {481-495},
Year = {2000},
Key = {Article}
}
@article{6490302,
Author = {Ser-Mien Chia and Jun Li and Xi Xu and Shujun Gao and Leong,
K.W. and Yu, H.},
Title = {Novel hepatocyte encapsulation enhances cellular
functions},
Journal = {Proceedings of the First Joint BMES/EMBS Conference. 1999
IEEE Engineering in Medicine and Biology 21st Annual
Conference and the 1999 Annual Fall Meeting of the
Biomedical Engineering Society (Cat. No.99CH37015)},
Volume = {vol.2},
Pages = {722 vol.2 -},
Address = {Atlanta, GA, USA},
Year = {1999},
url = {http://dx.doi.org/10.1109/IEMBS.1999.803877},
Keywords = {biological specimen preparation;biomedical
materials;cellular transport;encapsulation;liver;polymer
blends;proteins;},
Abstract = {We have synthesized a HEMA, MMA and MAA terpolymer to
complex with modified collagen for encapsulation of rat
hepatocytes. The encapsulated hepatocytes exhibited high
level of functions in culture comparable to those of
hepatocyte spheroids. The collagen that lined the inner
layer of the capsule provided a compatible substrate for
hepatocyte culture, and the outer terpolymer shell
determined permeability, which was optimized for transport
of 60 kDa but not 150 kDa molecules. Besides shorter
processing time than spheroid formation, the encapsulation
may offer other advantages important in designing a
bioartificial liver-assisted device},
Key = {6490302}
}
@article{Article,
Author = {Kalyanasundaram, S. and Feinstein, S. and Nicholson, J. P. and Leong, K. W. and Garver, R. I.},
Title = {Coacervate microspheres as carriers of recombinant
adenoviruses},
Journal = {Cancer Gene Therapy},
Volume = {6},
Number = {2},
Pages = {107-112},
Year = {1999},
Key = {Article}
}
@article{Article,
Author = {Truong-Le, V. L. and Walsh, S. M. and Schweibert, E. and Mao, H. Q. and Guggino, W. B. and August, J. T. and Leong,
K. W.},
Title = {Gene transfer by DNA-gelatin nanospheres},
Journal = {Archives of Biochemistry and Biophysics},
Volume = {361},
Number = {1},
Pages = {47-56},
Year = {1999},
Key = {Article}
}
@article{Article,
Author = {Roy, K. and Mao, H. Q. and Huang, S. K. and Leong, K.
W.},
Title = {Oral gene delivery with chitosan-DNA nanoparticles generates
immunologic protection in a murine model of peanut
allergy},
Journal = {Nature Medicine},
Volume = {5},
Number = {4},
Pages = {387-391},
Year = {1999},
Key = {Article}
}
@article{98084319706,
Author = {Leong, K. W. and Mao, H.-Q. and Truong-Le, V. L. and Roy,
K.},
Title = {DNA-polycation nanospheres as non-viral gene delivery
vehicles},
Journal = {Journal of Controlled Release},
Volume = {53},
Number = {1},
Pages = {183 -},
Year = {1998},
url = {http://dx.doi.org/10.1016/S0168-3659(97)00252-6},
Key = {98084319706}
}
@article{Article,
Author = {Truong-Le, V. L. and August, J. T. and Leong, K.
W.},
Title = {Controlled gene delivery by DNA-gelatin nanospheres},
Journal = {Human Gene Therapy},
Volume = {9},
Number = {12},
Pages = {1709-1717},
Year = {1998},
Key = {Article}
}
@article{Article,
Author = {Leong, K. W. and Mao, H. Q. and Truong-Le, V. L. and Roy, K. and Walsh, S. M. and August, J. T.},
Title = {DNA-polycation nanospheres as non-viral gene delivery
vehicles},
Journal = {Journal of Controlled Release},
Volume = {53},
Number = {1-3},
Pages = {183-193},
Year = {1998},
Key = {Article}
}
@article{Article,
Author = {Brown, K. E. and Leong, K. and Huang, C. H. and Dalal, R. and Green, G. D. and Haimes, H. B. and Jimenez, P. A. and Bathon, J.},
Title = {Gelatin/chondroitin 6-sulfate microspheres for the delivery
of therapeutic proteins to the joint},
Journal = {Arthritis and Rheumatism},
Volume = {41},
Number = {12},
Pages = {2185-2195},
Year = {1998},
Key = {Article}
}
@article{Article,
Author = {Hu, W. P. and Wang, L. F. and Leong, K. W.},
Title = {Synthesis and characterization of methacrylic derivatives as
drug carriers},
Journal = {Drug Development and Industrial Pharmacy},
Volume = {23},
Number = {7},
Pages = {671-678},
Year = {1997},
Key = {Article}
}
@article{Article,
Author = {Kalyanasundaram, S. and Leong, K. W.},
Title = {Intracranial drug delivery systems},
Journal = {Stp Pharma Sciences},
Volume = {7},
Number = {1},
Pages = {62-70},
Year = {1997},
Key = {Article}
}
@article{Article,
Author = {Kalyanasundaram, S. and Calhoun, V. D. and Leong, K.
W.},
Title = {A finite element model for predicting the distribution of
drugs delivered intracranially to the brain},
Journal = {American Journal of Physiology-Regulatory Integrative and
Comparative Physiology},
Volume = {42},
Number = {5},
Pages = {R1810-R1821},
Year = {1997},
Key = {Article}
}
@article{Article,
Author = {Kalyanasundaram, S. and Feinstein, S. and Nicholson, J. P. and Leong, K. W. and Garver, R. I.},
Title = {Recombinant adenovirus can be encapsulated and released from
coacervate microspheres in a time-dependent
fashion},
Journal = {Cancer Gene Therapy},
Volume = {4},
Number = {6},
Pages = {O40-O40},
Year = {1997},
Key = {Article}
}
@article{Article,
Author = {Lo, H. and Kadiyala, S. and Guggino, S. E. and Leong, K.
W.},
Title = {Poly(L-lactic acid) foams with cell seeding and
controlled-release capacity},
Journal = {Journal of Biomedical Materials Research},
Volume = {30},
Number = {4},
Pages = {475-484},
Year = {1996},
Key = {Article}
}
@article{96023040764,
Author = {Gutsche, Annie Tang and Lo, Hungnan and Zurlo, Joanne and Yager, James and Leong, Kam W.},
Title = {Engineering of a sugar-derivatized porous network for
hepatocyte culture},
Journal = {Biomaterials},
Volume = {17},
Number = {3},
Pages = {387 - 393},
Year = {1996},
url = {http://dx.doi.org/10.1016/0142-9612(96)85577-3},
Keywords = {Tissue;Cells;Porous materials;Sugar (sucrose);Foams;Hormones;Metabolism;Growth
kinetics;Polystyrenes;Morphology;Cytology;},
Abstract = {Many tissue engineering applications require a scaffold or
template conductive to cell attachment and maintenance of
functions. It may also be advantageous in some cases for
these scaffolds to have a controlled porous architecture to
facilitate cellular or tissue ingrowth. In this study, we
have engineered a porous carbohydrate-derivatized substrate
for hepatocyte culture. Polystyrene foams, with pore sizes
up to 100 μm, fabricated by phase separation from a
homogeneous naphthalene solution, were derivatized with
lactose and heparin, both of which are known to promote rat
hepatocyte attachment and maintenance of its differentiated
functions. Rat hepatocytes cultured on these derivatized
foams exhibited a rounded cellular morphology with many
microvilli evident on the surface of the cells. The
hepatocytes showed an increase in albumin secretion for the
first 3 days of culture in a defined, serum-free medium, and
dropped back to initial levels by the end of 7 days. The
production of cytochrome P<sub>450</sub>-dependent
hydroxytestosterone metabolites were also measured. Two
testosterone metabolites were maintained and five others
were present but decreased over a culture period of 1 week.
These carbohydrate-derivatized porous substrates may be
useful for large-scale culture of hepatocytes, toxicology
screening and for use in a liver assist device.},
Key = {96023040764}
}
@article{96123431325,
Author = {Kadiyala, S. and Lo, H. and Ponticiello, M.S. and Reddi,
A.H. and Leong, K.W.},
Title = {Bone induction achieved by controlled release of BMP from
PLA/hydroxyapatite foams},
Journal = {Transactions of the Annual Meeting of the Society for
Biomaterials in conjunction with the International
Biomaterials Symposium},
Volume = {1},
Pages = {289 -},
Address = {Toronto, Can},
Year = {1996},
Keywords = {Morphology;Organic acids;Phase separation;Cartilage;Scanning
electron microscopy;Porosimeters;Implants
(surgical);Proteins;Adsorption;Physiological models;Living
systems studies;},
Abstract = {In order to attain bone repair using bone morphogenic
proteins (BMP), there is a need for a carrier which can
effectively deliver the BMP to the repair site in a
controlled fashion and at the same time provide a scaffold
for the regenerating tissue to grow upon. The feasibility of
using BMP loaded polylactic acid (PLA)/hydroxyapatite (HA)
foam fabricated by a novel phase separation technique to
induce osteogenesis in an ectopic site in a rat model is
demonstrated. Results show that controlled release of BMP
from highly porous foams fabricated by the phase separation
technique is achieved. Furthermore implantation of these BMP
loaded foams in vivo resulted in the ectopic induction of
bone and cartilage.},
Key = {96123431325}
}
@article{96043147939,
Author = {Lo, H. and Kadiyala, S. and Guggino, S.E. and Leong,
K.W.},
Title = {Poly(L-lactic acid) foams with cell seeding and
controlled-release capacity},
Journal = {Journal of Biomedical Materials Research},
Volume = {30},
Number = {4},
Pages = {475 - 484},
Year = {1996},
url = {http://dx.doi.org/10.1002/(SICI)1097-4636(199604)30:4<475::AID-JBM5>3.0.CO;2-M},
Keywords = {Foams;Cells;Porous materials;Structure (composition);Growth
kinetics;Naphthalene;Thermoanalysis;Sublimation;Enzyme
kinetics;},
Abstract = {A synthetic porous 3-D structure that can mimic the
architecture of actual tissues, provide sustained release of
nutrients or growth factors, and serve as a template for
cell seeding would be an ideal substrate for tissue
engineering. Poly(1-lactic acid) foams were fabricated for
this purpose, based on the principle of phase separation
from homogeneous naphthalene solutions. Complex shapes could
be readily fabricated, and resulting foams had relatively
uniform, open cells throughout the matrix.},
Key = {96043147939}
}
@article{Article,
Author = {Gutsche, A. T. and Zurlo, J. and Deyesu, E. and Leong, K.
W.},
Title = {Rat hepatocyte morphology and function on
lactose-derivatized polystyrene surfaces},
Journal = {Biotechnology and Bioengineering},
Volume = {49},
Number = {3},
Pages = {259-265},
Year = {1996},
Key = {Article}
}
@article{Article,
Author = {Lesser, G. J. and Grossman, S. A. and Leong, K. W. and Lo,
H. N. and Eller, S.},
Title = {In vitro and in vivo studies of subcutaneous hydromorphone
implants designed for the treatment of cancer
pain},
Journal = {Pain},
Volume = {65},
Number = {2-3},
Pages = {265-272},
Year = {1996},
Key = {Article}
}
@article{Article,
Author = {Gutsche, A. T. and Lo, H. N. and Zurlo, J. and Yager, J. and Leong, K. W.},
Title = {Engineering of a sugar-derivatized porous network for
hepatocyte culture},
Journal = {Biomaterials},
Volume = {17},
Number = {3},
Pages = {387-393},
Year = {1996},
Key = {Article}
}
@article{Article,
Author = {Zhao, Z. and Leong, K. W.},
Title = {Controlled delivery of antigens and adjuvants in vaccine
development},
Journal = {Journal of Pharmaceutical Sciences},
Volume = {85},
Number = {12},
Pages = {1261-1270},
Year = {1996},
Key = {Article}
}
@article{Article,
Author = {Hollinger, J. O. and Leong, K.},
Title = {Poly(alpha-hydroxy acids): Carriers for bone morphogenetic
proteins},
Journal = {Biomaterials},
Volume = {17},
Number = {2},
Pages = {187-194},
Year = {1996},
Key = {Article}
}
@article{96083278395,
Author = {Leong, Kam W. and Mao, Haiquan and Zhuo,
Renxi},
Title = {Biodegradable polymers with a phosphoryl-containing
backbone: tissue engineering and controlled drug delivery
applications},
Journal = {Chinese Journal of Polymer Science (English
Edition)},
Volume = {13},
Number = {4},
Pages = {289 - 314},
Year = {1995},
Keywords = {Biomaterials;Biodegradation;Medical applications;Biocompatibility;Phosphorus;Controlled
drug delivery;Tissue;Bone;Grafts;Drug products;Molecular
structure;Synthesis (chemical);},
Abstract = {This review focuses on the potential of biodegradable
phosphoryl-containing polymers in medical applications.
These polymers are show to possess unique properties that
are yet to be fully understood. Many areas warrant further
investigation and much optimization remains to be done. The
fascinating chemistry of phosphorus poses interesting
hurdles but at the same time leaves ample room for polymer
scientists to exercise their creativity in designing
interesting biomaterials. As the mutual understanding
between basic and clinical scientists on the need of medical
devices and the capabilities of these new biomaterials
expands, imaginative application of new biomaterials to
other medical applications can be expected.},
Key = {96083278395}
}
@article{95072779323,
Author = {Dahiyat, B.I. and Posadas, E.M. and Hirosue, S. and Hostin,
E. and Leong, K.W.},
Title = {Degradable biomaterials with elastomeric characteristics and
drug-carrier function},
Journal = {Reactive Polymers},
Volume = {25},
Number = {2-3},
Pages = {101 - 109},
Year = {1995},
url = {http://dx.doi.org/10.1016/0923-1137(95)91297-P},
Keywords = {Biomaterials;Controlled drug delivery;Elastomers;Polyesters;Biodegradation;Medicine;Medical
applications;Amino acids;},
Abstract = {The design of drug-carrying elastomers based on
poly(phosphoester-urethanes) (PPUs) is presented.
Bis(2-hydroxyethyl)phosphite and bis(6-hydroxyhexyl)phosphite
were used as the chain extenders and 1,4-butane diisocyanate
was the basis of the hard segment. The labile phosphoester
linkage in the backbone of the PPU confers biodegradability
on the polymer. Using the reactive phosphite side chain in
the PPUs, p-aminosalicylic acid and benzocaine were attached
pendantly to the polymer with or without a spacer. In vitro
release of both drugs was complete in several hours. In
contrast, ethambutol incorporated into the backbone of the
polymer was released in over 10 days. Preliminary
cytotoxicity of the drug-carrier to a macrophage cell line
was also assessed.},
Key = {95072779323}
}
@article{96033072629,
Author = {Dahiyat, B. I. and Richards, M. and Leong, K.
W.},
Title = {Controlled release from poly(phosphoester)
matrices},
Journal = {Journal of Controlled Release},
Volume = {33},
Number = {1},
Pages = {13 -},
Year = {1995},
url = {http://dx.doi.org/10.1016/0168-3659(94)00039-W},
Key = {96033072629}
}
@article{Article,
Author = {Leong, K. W. and Mao, H. Q. and Zhuo, R.
X.},
Title = {Biodegradable polymers with a phosphoryl-containing
backbone: Tissue engineering and controlled drug delivery
applications},
Journal = {Chinese Journal of Polymer Science},
Volume = {13},
Number = {4},
Pages = {289-314},
Year = {1995},
Key = {Article}
}
@article{95112932670,
Author = {Brown, K.E. and Bathon, J. and Huang, C.H. and Dalal, R. and Leong, K.W.},
Title = {Cationic gelatin as a gene carrier},
Journal = {Materials Research Society Symposium - Proceedings},
Volume = {394},
Pages = {61 - 66},
Address = {San Francisco, CA, USA},
Year = {1995},
Keywords = {Genes;Cells;Synthesis (chemical);Complexation;DNA;Drug
products;Toxicity;Bioassay;},
Abstract = {Cationic gelatin (CG) has been evaluated as a non-viral
vector for cell transfection. CG is synthesized by modifying
gelatin with hexanediamine. Its complexation with psv-8-gal
plasmid caused an electrophoretic mobility shift of the
plasmid. CG/DNA complexes are optimized in terms of
transfection efficiency in CHODUK XB1 and COS 7 cell lines.
Maximal gene expression for both cell types occurred in
serum free medium with chloroquine at cationic gelatin/DNA
ratios of about two and seven. Compared to DEAF dextran,
polysine and Lipofectamine, CG is the most efficient in
transfecting COS 7 cells. In a dye reduction cytotoxicity
assay, CG caused <5% of cells to become nonviable at a
concentration of 100 μg/m1, while other transfection
reagents tested caused 25-100% of cell death.},
Key = {95112932670}
}
@article{95112932690,
Author = {Shao, Wen and Leong, Kam W.},
Title = {Enzymatically degradable synthetic polymers},
Journal = {Materials Research Society Symposium - Proceedings},
Volume = {394},
Pages = {199 - 204},
Address = {San Francisco, CA, USA},
Year = {1995},
Keywords = {Biodegradation;Controlled drug delivery;Polyelectrolytes;Synthesis
(chemical);Monomers;Polymerization;Gel permeation
chromatography;},
Abstract = {Complex coacervation is an appealing method of
microencapsulating delicate proteins for controlled drug
delivery. Natural polyelectrolytes, such as collagen,
gelatin, hyaluronic acid, and chondroitin sulfate, are
popular choices for formulating the microspheres. For
advantage of versatility, synthetic systems are attractive.
Typical synthetic polyelectrolytes are composed of a
carbon-carbon backbone that is non-biodegradable. To design
synthetic polyelectrolytes that are biodegradable, we
synthesized diamines containing dipeptide or tripeptide
sequences that are enzymatically degradable. The
enzymatically degradable linkages comprised gly-phe,
gly-phe-phe, or gly-gly-phe, and lysine and
2,3-diaminopropionic acid co-monomers served as the charged
component. Using an interfacial polymerization technique,
these monomers were condensed with diacyl chlorides,
including succinyl, adipoyl, or terephthaloyl chloride to
form polyamides. Results of gel permeation chromatography
and ninhydrin assays showed that the polymers degraded in
PBS containing α-chymotrypsin.},
Key = {95112932690}
}
@article{Article,
Author = {Dahiyat, B. I. and Richards, M. and Leong, K.
W.},
Title = {Controlled-Release from Poly(Phosphoester)
Matrices},
Journal = {Journal of Controlled Release},
Volume = {33},
Number = {1},
Pages = {13-21},
Year = {1995},
Key = {Article}
}
@article{95112932867,
Title = {Proceedings of the 1995 MRS Spring Meeting},
Journal = {Materials Research Society Symposium - Proceedings},
Volume = {394},
Pages = {206 -},
Address = {San Francisco, CA, USA},
Editor = {Mikos, Antonios G.;Leong and Kam W.;Yaszemski and Michael
J.;Tamada, Janet A.;Radomsky and Michael L.;},
Year = {1995},
Keywords = {Medical applications;Surgery;Biopolymers;Orthopedics;Biomaterials;Controlled
drug delivery;Tissue;Synthesis (chemical);Gels;Physical
properties;Biological materials;},
Abstract = {The proceedings contains 30 papers. Topics discussed include
polymers for orthopedic and reconstructive surgery,
polymeric applications for drug delivery and tissue
engineering, synthesis and characterization of biomedical
polymers.},
Key = {95112932867}
}
@article{Article,
Author = {Reisfeld, B. and Kalyanasundaram, S. and Leong,
K.},
Title = {A Mathematical-Model of Polymeric Controlled Drug-Release
and Transport in the Brain},
Journal = {Journal of Controlled Release},
Volume = {36},
Number = {3},
Pages = {199-207},
Year = {1995},
Key = {Article}
}
@article{Article,
Author = {Dahiyat, B. I. and Posadas, E. M. and Hirosue, S. and Hostin, E. and Leong, K. W.},
Title = {Degradable Biomaterials with Elastomeric Characteristics and
Drug-Carrier Function},
Journal = {Reactive Polymers},
Volume = {25},
Number = {2-3},
Pages = {101-109},
Year = {1995},
Key = {Article}
}
@article{Article,
Author = {Shao, W. and Leong, K. W.},
Title = {Microcapsules Obtained from Complex Coacervation of Collagen
and Chondroitin Sulfate},
Journal = {Journal of Biomaterials Science-Polymer Edition},
Volume = {7},
Number = {5},
Pages = {389-399},
Year = {1995},
Key = {Article}
}
@article{94091391833,
Author = {Brown, Kimberly E. and Shao, Wen and Bathon, Joan and Leong,
Kam W.},
Title = {Controlled drug delivery to the joints by enzymatically
degradable microspheres},
Journal = {Materials Research Society Symposium Proceedings},
Volume = {331},
Pages = {73 - 78},
Address = {Boston, MA, USA},
Year = {1994},
Keywords = {Joints (anatomy);Biodegradation;Biomedical
engineering;Biopolymers;Polyelectrolytes;Reaction
kinetics;Crosslinking;Enzymes;},
Abstract = {An intra-articular polymeric controlled release system was
developed that is tailored to, and responsive to, the
intensity of joint inflammation. Microspheres composed of
the naturally occurring polyelectrolytes, gelatin and
chondroitin sulfate, were synthesized by complex
coacervation and the kinetics of release of encapsulated
<sup>14</sup>C-catalase, was evaluated in vitro in the
presence of inflammatory and non-inflammatory human joint
fluids. The relative activity of gelatinase, a
metalloprotease enzyme, was quantified in each of the joints
fluids. Rate of degradation of microspheres, and consequent
release of <sup>14</sup>C-catalase, was found to parallel
the relative gelatinase activities in the joint fluids.
Furthermore, various methods of crosslinking were found to
affect the kinetics of microsphere degradation in the
fluids. A catalase loading level of up to 28% was achieved,
and the encapsulated catalase was found to retain up to 58%
of its biological activity.},
Key = {94091391833}
}
@article{94071340784,
Author = {Gutsche, A.T. and Parsons-Wingerter, P. and Chand, D. and Saltzman, W.M. and Leong, K.W.},
Title = {N-acetylglucosamine and adenosine derivatized surfaces for
cell culture: 3T3 fibroblast and chicken hepatocyte
response},
Journal = {Biotechnology and Bioengineering},
Volume = {43},
Number = {8},
Pages = {801 - 809},
Year = {1994},
Keywords = {Tissue;Biotechnology;Biomaterials;Growth
kinetics;Biocompatibility;},
Abstract = {3T3 fibroblasts and primary chicken hepatocytes were
cultured on derivatized polystyrene surfaces to examine the
effect of cell specific ligands of cellular morphology and
growth. Fibroblasts grew avidly on the microcarriers,
whereas chicken hepatocytes adhered well to and formed large
aggregates around the microcarriers.},
Key = {94071340784}
}
@article{94091391828,
Author = {Lo, H. and Kadiyala, S. and Guggino, S.E. and Leong,
K.W.},
Title = {Biodegradable foams for cell transplantation},
Journal = {Materials Research Society Symposium Proceedings},
Volume = {331},
Pages = {41 - 46},
Address = {Boston, MA, USA},
Year = {1994},
Keywords = {Transplantation (surgical);Biopolymers;Biomaterials;Biodegradation;Cells;Foamed
plastics;Drug products;Porosity;Morphology;Microstructure;},
Abstract = {A processing technique based on the principle of phase
separation was developed to fabricate three-dimensional
microcellular foams to act as templates for cell
transplantation. The polymers used to make the foams were
polylactic acid (PLLA) and a polyphosphoester (BPA/ PP). The
resulting foams had relatively uniform, open cells
throughout the matrix. The foams could also be fabricated
into complex shapes to meet specific design requirements.
The foam morphology and microstructure were characterized by
mercury porosimetry and scanning electron microscopy.
Osteoblast like cells ROS17/2.8 were successfully cultured
in the foams. Cell attachment to the foam interior was
verified by confocal microscopy.The fabrication technique
allows incorporation of drugs or nutrients into the highly
porous structure as demonstrated by the intimate dispersion
of fluorescein isothiocyanate (FITC) in the
matrix.},
Key = {94091391828}
}
@article{94122453031,
Author = {Tang Gutsche and Annie and Zurlo, Joanne and Lo, Hungnan and Leong, Kam W.},
Title = {Synthesis and characterization of polymer substrates for rat
hepatocyte culture},
Journal = {Materials Research Society Symposium - Proceedings},
Volume = {330},
Pages = {243 - 248},
Address = {Boston, MA, USA},
Year = {1994},
Keywords = {Synthesis (chemical);Characterization;Substrates;Animal cell
culture;Enzymes;Amino acids;Polysaccharides;Tissue;Foams;Three
dimensional;},
Abstract = {Lactose and heparin were covalently coupled to
poly(chloromethyl styrene) and the modified polymer was used
as a substrate for rat hepatocyte culture. Lactose and
heparin are recognized by rat hepatocytes and can be used to
mediate cell attachment to the substrate. Rat hepatocytes
cultured in serum-free media on these substrates were able
to maintain enzymes and peptides important in the
detoxification functions of hepatocytes, without the
addition of hormones such as dexamethasone, media additives
such as DMSO, or complex biological extracellular factors.
The growing interest in large-scale cell culture and in
tissue engineering requires substrates of different
geometries. Therefore, we have fabricated the derivatized
polymers into microcarriers and, most recently, foams. These
three-dimensional structures, combined with the chemistries
of the polymers, provided the hepatocytes with more
cell-cell interactions and in vivo-like geometries than
conventional flat-dish culture.},
Key = {94122453031}
}
@article{95012534844,
Author = {Lin, Steve T. and Krebs, Steve L. and Kadiyala, Sudha and Leong, Kam W. and LaCourse, William C. and Kumar,
Binod},
Title = {Development of bioabsorbable glass fibres},
Journal = {Biomaterials},
Volume = {15},
Number = {13},
Pages = {1057 - 1061},
Year = {1994},
url = {http://dx.doi.org/10.1016/0142-9612(94)90091-4},
Keywords = {Phosphates;Iron oxides;Dissolution;Strength of
materials;Biocompatibility;Biodegradation;Tissue;Thermodynamic
properties;Bone;Tensile strength;},
Abstract = {Calcium-iron phosphate glasses with an iron oxide content
ranging from 5 wt.% to 22 wt.% were prepared to investigate
the effect of iron oxide on the properties of the glass. It
was found that the dissolution rate, the fibre strength and
the glass transition temperature were strongly affected by
iron oxide. The glass dissolution rate exhibited a 50-fold
reduction while the fibre strength doubled when the iron
oxide content was increased from 5 wt.% to 22 wt.%. The
phosphate glass containing 22 wt.% of iron oxide had a
dissolution rate of about 5 μg/(cm<sup>2</sup> day). The
fibres drawn from this glass also exhibited the highest
tensile strength over 1000 MPa. A cortical bone plug method
was used to assess the biocompatibility of the glasses with
the hard and soft tissues. The tissues surrounding the
samples showed no inflammation at 9 wk.},
Key = {95012534844}
}
@article{Article,
Author = {Lin, S. T. and Krebs, S. L. and Kadiyala, S. and Leong, K.
W. and Lacourse, W. C. and Kumar, B.},
Title = {Development of Bioabsorbable Glass-Fibers},
Journal = {Biomaterials},
Volume = {15},
Number = {13},
Pages = {1057-1061},
Year = {1994},
Key = {Article}
}
@article{Article,
Author = {Uppal, P. and Jampel, H. D. and Quigley, H. A. and Leong, K.
W.},
Title = {Pharmacokinetics of Etoposide Delivery by a Bioerodible Drug
Carrier Implanted at Glaucoma Surgery},
Journal = {Journal of Ocular Pharmacology},
Volume = {10},
Number = {2},
Pages = {471-479},
Year = {1994},
Key = {Article}
}
@article{Article,
Author = {Gutsche, A. T. and Parsonswingerter, P. and Chand, D. and Saltzman, W. M. and Leong, K. W.},
Title = {N-Acetylglucosamine and Adenosine Derivatized Surfaces for
Cell-Culture - 3t3 Fibroblast and Chicken Hepatocyte
Response},
Journal = {Biotechnology and Bioengineering},
Volume = {43},
Number = {8},
Pages = {801-809},
Year = {1994},
Key = {Article}
}
@article{Article,
Author = {Kalyanasundaram, S. and Calhoun, V. D. and Leong, K.
W.},
Title = {Coupled Convective-Diffusive Mass-Transport in the
Brain},
Journal = {Faseb Journal},
Volume = {8},
Number = {4},
Pages = {A14-A14},
Year = {1994},
Key = {Article}
}
@article{Article,
Author = {Golumbek, P. T. and Azhari, R. and Jaffee, E. M. and Levitsky, H. I. and Lazenby, A. and Leong, K. and Pardoll,
D. M.},
Title = {Controlled-Release, Biodegradable Cytokine Depots - a New
Approach in Cancer Vaccine Design},
Journal = {Cancer Research},
Volume = {53},
Number = {24},
Pages = {5841-5844},
Year = {1993},
Key = {Article}
}
@article{Article,
Author = {Dahiyat, B. I. and Hostin, E. and Posadas, E. M. and Leong,
K. W.},
Title = {Synthesis and Characterization of Putrescine-Based
Poly(Phosphoester-Urethanes)},
Journal = {Journal of Biomaterials Science-Polymer Edition},
Volume = {4},
Number = {5},
Pages = {529-543},
Year = {1993},
Key = {Article}
}
@article{Article,
Author = {Leong, K. W. and Truong, V. L.},
Title = {P-Glycoprotein-Specific Binding of Immuno-Microspheres to
Drug-Resistant Kb-V-1 Cells},
Journal = {Faseb Journal},
Volume = {7},
Number = {4},
Pages = {A690-A690},
Year = {1993},
Key = {Article}
}
@article{Article,
Author = {Jampel, H. D. and Thibault, D. and Leong, K. W. and Uppal,
P. and Quigley, H. A.},
Title = {Glaucoma Filtration Surgery in Nonhuman-Primates Using Taxol
and Etoposide in Polyanhydride Carriers},
Journal = {Investigative Ophthalmology & Visual Science},
Volume = {34},
Number = {11},
Pages = {3076-3083},
Year = {1993},
Key = {Article}
}
@article{Article,
Author = {Reisfeld, B. and Blackband, S. and Calhoun, V. and Grossman,
S. and Eller, S. and Leong, K.},
Title = {The Use of Magnetic-Resonance-Imaging to Track Controlled
Drug Release and Transport in the Brain},
Journal = {Magnetic Resonance Imaging},
Volume = {11},
Number = {2},
Pages = {247-252},
Year = {1993},
Key = {Article}
}
@article{Article,
Author = {Heffez, D. S. and Leong, K. W.},
Title = {Sustained-Release of Papaverine for the Treatment of
Cerebral Vasospasm - Invitro Evaluation of Release Kinetics
and Biological-Activity},
Journal = {Journal of Neurosurgery},
Volume = {77},
Number = {5},
Pages = {783-787},
Year = {1992},
Key = {Article}
}
@article{91080266759,
Author = {Richards, M. and Dahiyat, B.I. and Arm, D.M. and Lin, S. and Leong, K.W.},
Title = {Interfacial polycondensation and characterization of
polyphosphates and polyphosphonates},
Journal = {Journal of Polymer Science, Part A: Polymer
Chemistry},
Volume = {29},
Number = {8},
Pages = {1157 - 1165},
Year = {1991},
url = {http://dx.doi.org/10.1002/pola.1991.080290809},
Keywords = {Polymerization - Condensation Reactions;Chemical Reactions -
Reaction Kinetics;},
Abstract = {The synthesis of four bisphenol A-based polyphosphates and
phosphonates was accomplished. The polymerization involved a
condensation between bisphenol A and a phosphorodichloridate.
The heterophasic polycondensation technique was used with
the aid of a phase transfer catalyst to yield molecular
weights in the range of 20,000-40,000. The polymers were
characterized by FT-IR, FT-NMR, and DSC. Systematic studies
on the interfacial polymerization indicated that a more
concentrated organic phase and a slight excess of diol
favored the production of high molecular weight polymers. An
optimum concentration of 5-10 mol % was observed for three
different phase transfer catalysts. Kinetic studies showed
that the polymerization was complete within the first 10
min. The degree of agitation was shown to be important, as
the overhead mechanical stirrer was not as effective as the
blender. In addition, crosslinking with pentaerythritol
yielded significant increases in the molecular weights of
these polymers.},
Key = {91080266759}
}
@article{Article,
Author = {Jampel, H. D. and Koya, P. and Leong, K. and Quigley, H.
A.},
Title = {Invitro Release of Hydrophobic Drugs from Polyanhydride
Disks},
Journal = {Ophthalmic Surgery and Lasers},
Volume = {22},
Number = {11},
Pages = {676-680},
Year = {1991},
Key = {Article}
}
@article{Article,
Author = {Saltzman, W. M. and Parsonswingerter, P. and Leong, K. W. and Lin, S.},
Title = {Fibroblast and Hepatocyte Behavior on Synthetic-Polymer
Surfaces},
Journal = {Journal of Biomedical Materials Research},
Volume = {25},
Number = {6},
Pages = {741-759},
Year = {1991},
Key = {Article}
}
@article{91100307733,
Author = {Richards, M. and Dahiyat, B.I. and Arm, D.M. and Brown, P.R. and Leong, K.W.},
Title = {Evaluation of polyphosphates and polyphosphonates as
degradable biomaterials},
Journal = {Journal of Biomedical Materials Research},
Volume = {25},
Number = {9},
Pages = {1151 - 1167},
Year = {1991},
Keywords = {Polymers--Degradation;Plastics--Medical Applications;},
Abstract = {A series of polymers, bisphenol A-based poly(phosphoesters),
were evaluated as degradable biomaterials. Degradation was
observed for the four polymers studied under both in vitro
and in vivo conditions. The rate of degradation was affected
by polymer side-chain structure and correlated with the
swelling behavior. The ethyl side-chain polymers absorbed
more water than their phenyl counterparts. Among the
sterilization methods, UV irradiation followed by antibiotic
treatment was the most suitable, as steam autoclave and
ethylene oxide treatments altered the properties of several
of the poly(phosphoesters). Tissue response to the
poly(phosphoesters) in rabbits was characterized by minor
encapsulation and slight or no lymphocyte, giant cell, or
macrophage activity. No evidence of edema or necrosis was
found. The elastic moduli of these materials varied from 488
MPa for poly(bisphenol A-ethylphosphate) (BPA/EOP) to 627
MPa for the more rigid poly(bisphenol A-phenylphosphonate)
(BPA/PP). The ultimate strength, modulus, and energy to
failure of BPA/PP were lower than those of similarly
compression molded high-molecular-weight poly(L-lactic acid)
(PLLA).},
Key = {91100307733}
}
@article{91080266982,
Author = {Saltzman, W. Mark and Parsons-Wingerter, Patricia and Leong,
Kam W. and Lin, Shin},
Title = {Fibroblast and hepatocyte behavior on synthetic polymer
surfaces},
Journal = {Journal of Biomedical Materials Research},
Volume = {25},
Number = {6},
Pages = {741 - 759},
Year = {1991},
Keywords = {Copolymers--Medical Applications;Biological
Materials--Cells;Polymers--Surfaces;},
Abstract = {Biodegradable poly(phosphoesters) with varying side group
chemistry and copolymers of styrene and methyl vinyl ketone
(MVK) with varying degrees of hydrophobicity were used to
study the growth and behavior of surface-attached
fibroblasts and hepatocytes. Mouse 3T3 fibroblasts and
chicken embryo fibroblasts attached and proliferated on all
of the polymers tested. Fewer cells attached to copolymers
of styrene and MVK than to glass or tissue culture
polystyrene controls; cell attachment to several
poly(phosphoester) surfaces was indistinguishable from
controls. The mean speed of fibroblast migration was faster
on surfaces where fewer cells attached (59 to 84 μm/h on
low attachment surfaces compared with 40 to 46 μm/h on
high attachment surfaces). When surface-attached cells were
stained with fluorescently labeled phalloidin, only a
fraction of the cells on low attachment surfaces were shown
to have prominent arrays of actin filament bundles. Chicken
hepatocytes also attached to the polymer surfaces. When a
suspension containing a large number of cells was placed
over the polymer surfaces, approximately 50% of the
hepatocytes attached during the first 9 h. Surprisingly,
hepatocyte attachment and viability in culture were
relatively insensitive to the chemistry of the synthetic
polymer substrates. Cell number increased by about a factor
of 2 over the first 48 h of culture, then decreased back to
approximately 50% of initial cell number over the next
several days. Cell morphology did depend on the chemical
structure of the substrates.},
Key = {91080266982}
}
@article{Article,
Author = {Richards, M. and Dahiyat, B. I. and Arm, D. M. and Brown, P.
R. and Leong, K. W.},
Title = {Evaluation of Polyphosphates and Polyphosphonates as
Degradable Biomaterials},
Journal = {Journal of Biomedical Materials Research},
Volume = {25},
Number = {9},
Pages = {1151-1167},
Year = {1991},
Key = {Article}
}
@article{Article,
Author = {Charles, J. B. and Ganthier, R. and Wilson, M. R. and Lee,
D. A. and Baker, R. S. and Leong, K. W. and Glasgow, B.
J.},
Title = {Use of Bioerodible Polymers Impregnated with Mitomycin in
Glaucoma Filtration Surgery in Rabbits},
Journal = {Ophthalmology},
Volume = {98},
Number = {4},
Pages = {503-508},
Year = {1991},
Key = {Article}
}
@article{Article,
Author = {Koya, P. and Jampel, H. and Quigley, H. and Leong,
K.},
Title = {Pharmacokinetics of Vp-16 Release from Polyanhydrides after
Experimental Filtration Surgery},
Journal = {Investigative Ophthalmology & Visual Science},
Volume = {32},
Number = {4},
Pages = {745-745},
Year = {1991},
Key = {Article}
}
@article{Article,
Author = {Shi, F. Y. and Wang, L. F. and Tashev, E. and Leong, K.
W.},
Title = {Synthesis and Characterization of Hydrolytically Labile
Poly(Phosphoester Urethanes)},
Journal = {Acs Symposium Series},
Volume = {469},
Pages = {141-154},
Year = {1991},
Key = {Article}
}
@article{Article,
Author = {Lewis, H. and Schwartz, S. and Lee, D. and Leong,
K.},
Title = {The Use of Bioerodible Polymer and 5-Fluorouracil in the
Treatment of Experimental Proliferative Vitreoretinopathy},
Journal = {Investigative Ophthalmology & Visual Science},
Volume = {32},
Number = {4},
Pages = {1047-1047},
Year = {1991},
Key = {Article}
}
@article{Article,
Author = {Richards, M. and Dahiyat, B. I. and Arm, D. M. and Lin, S. and Leong, K. W.},
Title = {Interfacial Polycondensation and Characterization of
Polyphosphates and Polyphosphonates},
Journal = {Journal of Polymer Science Part a-Polymer
Chemistry},
Volume = {29},
Number = {8},
Pages = {1157-1165},
Year = {1991},
Key = {Article}
}
@article{90110437615,
Author = {Shi, F.Y. and Wang, L.F. and Leong, K.W.},
Title = {Synthesis and characterization of hydrolytically labile
polyurethanes},
Journal = {Polymer Preprints, Division of Polymer Chemistry, American
Chemical Society},
Volume = {31},
Number = {2},
Pages = {177 -},
Address = {Washington, DC, USA},
Year = {1990},
Keywords = {Polymers--Synthesis;Lipids--Chemical Reactions;Chemical
Reactions--Hydrolysis;Drug Products--Controlled
Delivery;},
Abstract = {Polyurethane has been extensively studied and widely used as
a biomedical material since the early 1960s. We have been
designing biodegradable polyurethanes that contain a
phosphorus ester linkage in the backbone to induce
biodegradability and to link bioactive agents directly to
the phosphorus atom. In this communication, we extend this
study to polyurethanes which contain phospholipids in the
side chain. Furthermore, with the objective of obtaining a
polymer that would break down into non-toxic products, a
lysine-based diisocyanate and a biodegradable chain extender
are used for the polyurethane synthesis.},
Key = {90110437615}
}
@article{91010085108,
Author = {Tashev, E. and Shi, F.Y. and Leong, K.W.},
Title = {Potential applications of poly(phosphoester-urethanes) in
controlled drug delivery},
Journal = {Polymeric Materials Science and Engineering, Proceedings of
the ACS Division of Polymeric Materials Science and
Engineering},
Volume = {63},
Pages = {43 - 46},
Address = {Washington, DC, USA},
Year = {1990},
Keywords = {Polyesters - Biodegradation;Drug Products - Controlled
Delivery;},
Abstract = {In the past few years we have been studying the potential of
poly(phosphoesters) as biomaterials, including applications
in drug delivery. These polymers allow direct linkage of
bioactive compounds to the phosphorus atom to form a pendant
release system. The biodegradability of these polymers stems
from the hydrolytically vulnerable phosphoester bond in the
backbone. Polyurethane on the other hand is biostable. It
has superior physical properties and has been extensively
studied for biomedical applications. To combine
biodegradability and desirable mechanical strength, we
examine the synthesis and characterization of polyurethanes
which include a phosphoester bond in the
backbone.},
Key = {91010085108}
}
@article{Article,
Author = {Jampel, H. D. and Leong, K. W. and Dunkelburger, G. R. and Quigley, H. A.},
Title = {Glaucoma Filtration Surgery in Monkeys Using 5-Fluorouridine
in Polyanhydride Disks},
Journal = {Archives of Ophthalmology},
Volume = {108},
Number = {3},
Pages = {430-435},
Year = {1990},
Key = {Article}
}
@article{91030161501,
Author = {Wong, Ngai C. and Leong, K. W. and Shapiro, Jeffrey
H.},
Title = {Nonclassical intensity correlation from a type I phase
matched optical parametric oscillator},
Pages = {68 - 70},
Address = {Anaheim, CA, USA},
Year = {1990},
Keywords = {Oscillators;Noise, Spurious Signal--Shot Noise;Quantum
Theory;},
Abstract = {The observation of nonclassical correlation in the
intensities of the nondegenerate signal and idler outputs
from an optical parametric oscillator (OPO) is reported. The
CW OPO consists of a 25-mm-long, type-I, phase-matched
LiNbO<sub>3</sub>:MgO crystal inside a single-ended cavity,
which is resonant for both the signal and idler. The output
coupling for the IR signal and idler is approximately 4.5%,
and the internal round trip power loss is estimated to be
1.9%. The detected signal and idler are amplified,
differenced, and compared to the shot-noise level provided
by two light bulbs having the same DC photocurrents. A
broadband intensity correlation is observed over a frequency
range from 0.8 to 5 MHz. The maximum correlation, which
occurs at approximately 1.5 MHz, yields a noise level 45%
below shot noise. The estimated system efficiency of 83%
then implies a generated noise suppression of 55%. Below 800
kHz, the difference intensity noise is dominated by 1/f-type
excess noise. A linearized quantum analysis of the doubly
resonant OPO, including the effects of the pump noise, shows
that at low frequencies the pump noise may impose a limit on
the maximum noise suppression.},
Key = {91030161501}
}
@article{90070429299,
Author = {Leong, Kam W.},
Title = {Poly(phosphoesters) as biomaterials},
Journal = {Polymer Preprints, Division of Polymer Chemistry, American
Chemical Society},
Volume = {31},
Number = {1},
Pages = {251 -},
Address = {Boston, MA, USA},
Year = {1990},
Keywords = {Biopolymers--Applications;},
Abstract = {In designing new biomaterials for various biomedical
applications, the author has been working on a class of
polymers which contain a phosphorus ester linkage in the
backbone. These polymers are potentially biodegradable
because of the physiologically labile phosphorus ester
linkage in the backbone. Theoretically the polymer would
break down into phosphate, a diol, and another alcohol if
the side chain is a phosphate ester bond. Most of the
physical and biological characterizations have been
performed on the bisphenol-A based poly(phosphoesters).},
Key = {90070429299}
}
@article{Article,
Author = {Tamargo, R. J. and Leong, K. W. and Brem,
H.},
Title = {Growth-Inhibition of the 9l Glioma Using Polymers to Release
Heparin and Cortisone-Acetate},
Journal = {Journal of Neuro-Oncology},
Volume = {9},
Number = {2},
Pages = {131-138},
Year = {1990},
Key = {Article}
}
@article{Article,
Author = {Brem, H. and Kader, A. and Epstein, J. I. and Tamargo, R. J. and Domb, A. and Langer, R. and Leong, K.
W.},
Title = {Biocompatibility of a Biodegradable, Controlled-Release
Polymer in the Rabbit Brain},
Journal = {Selective Cancer Therapeutics},
Volume = {5},
Number = {2},
Pages = {55-65},
Year = {1989},
Key = {Article}
}
@article{Article,
Author = {Kost, J. and Leong, K. and Langer, R.},
Title = {Ultrasound-Enhanced Polymer Degradation and Release of
Incorporated Substances - (Controlled Release Drug Delivery
Systems)},
Journal = {Proceedings of the National Academy of Sciences of the
United States of America},
Volume = {86},
Number = {20},
Pages = {7663-7666},
Year = {1989},
Key = {Article}
}
@article{Article,
Author = {Kost, J. and Leong, K. and Langer, R.},
Title = {Ultrasonically Controlled Polymeric Drug
Delivery},
Journal = {Makromolekulare Chemie-Macromolecular Symposia},
Volume = {19},
Pages = {275-285},
Year = {1988},
Key = {Article}
}
@article{Article,
Author = {Bindschaedler, C. and Leong, K. and Mathiowitz, E. and Langer, R.},
Title = {Polyanhydride Microsphere Formulation by
Solvent-Extraction},
Journal = {Journal of Pharmaceutical Sciences},
Volume = {77},
Number = {8},
Pages = {696-698},
Year = {1988},
Key = {Article}
}
@article{Article,
Author = {Lee, D. A. and Leong, K. W. and Panek, W. C. and Eng, C. T. and Glasgow, B. J.},
Title = {The Use of Bioerodible Polymers and 5-Fluorouracil in
Glaucoma Filtration Surgery},
Journal = {Investigative Ophthalmology & Visual Science},
Volume = {29},
Number = {11},
Pages = {1692-1697},
Year = {1988},
Key = {Article}
}
@article{Article,
Author = {Lee, D. A. and Flores, R. A. and Anderson, P. J. and Leong,
K. W. and Teekhasaenee, C. and Dekater, A. W. and Hertzmark,
E.},
Title = {Glaucoma Filtration Surgery in Rabbits Using Bioerodible
Polymers and 5-Fluorouracil},
Journal = {Ophthalmology},
Volume = {94},
Number = {12},
Pages = {1523-1530},
Year = {1987},
Key = {Article}
}
@article{Article,
Author = {Leong, K. W. and Simonte, V. and Langer,
R.},
Title = {Synthesis of Polyanhydrides - Melt-Polycondensation,
Dehydrochlorination, and Dehydrative Coupling},
Journal = {Macromolecules},
Volume = {20},
Number = {4},
Pages = {705-712},
Year = {1987},
Key = {Article}
}
@article{86020018194,
Author = {Leong, K. W. and D'Amore, P. and Marletta, M. and Langer,
R.},
Title = {BIOERODIBLE POLYANHYDRIDES AS DRUG-CARRIER MATRICES. II.
BIOCOMPATIBILITY AND CHEMICAL REACTIVITY.},
Journal = {Journal of Biomedical Materials Research},
Volume = {20},
Number = {1},
Pages = {51 - 64},
Year = {1986},
Keywords = {BIOMEDICAL ENGINEERING - Surgical Implants;DRUG PRODUCTS -
Encapsulation;CHEMICAL REACTIONS - Research;},
Abstract = {The biocompatibility of bioerodible polyanhydrides and
toxicology of the polymer breakdown products were assessed.
The polymer did not provoke inflammatory responses in the
corneas of rabbits over a six week implantation period. The
degradation products of the polymers were nonmutagenic,
noncytotoxic, and had a low teratogenic potential. The in
vitro growth of mammalian cells on the polymers was
unaffected as measured by cell morphology and cell growth
rate. The chemical reactivity of the polyanhydrides with
reactive model drugs, para substituted anilines, was also
examined. No reaction occurred between the polymer and the
drug during the hydrolytic degradation of the matrix at 37
degree C.},
Key = {86020018194}
}
@article{Article,
Author = {Leong, K. W. and Damore, P. and Marletta, M. and Langer,
R.},
Title = {Bioerodible Polyanhydrides as Drug-Carrier Matrices .2.
Biocompatibility and Chemical-Reactivity},
Journal = {Journal of Biomedical Materials Research},
Volume = {20},
Number = {1},
Pages = {51-64},
Year = {1986},
Key = {Article}
}
@article{Article,
Author = {Leong, K. W. and Kost, J. and Mathiowitz, E. and Langer,
R.},
Title = {Polyanhydrides for Controlled Release of Bioactive
Agents},
Journal = {Biomaterials},
Volume = {7},
Number = {5},
Pages = {364-371},
Year = {1986},
Key = {Article}
}
@article{Article,
Author = {Langer, R. and Siegel, R. and Brown, L. and Leong, K. and Kost, J. and Edelman, E.},
Title = {Controlled Release - 3 Mechanisms},
Journal = {Chemtech},
Volume = {16},
Number = {2},
Pages = {108-110},
Year = {1986},
Key = {Article}
}
@article{85110160759,
Author = {Leong, K. W. and Brott, B. C. and Langer,
R.},
Title = {BIOERODIBLE POLYANHYDRIDES AS DRUG-CARRIER MATRICES. I:
CHARACTERIZATION, DEGRADATION, AND RELEASE
CHARACTERISTICS.},
Journal = {Journal of Biomedical Materials Research},
Volume = {19},
Number = {8},
Pages = {941 - 955},
Year = {1985},
Keywords = {POLYMERS - Biodegradation;PLASTICS - Injection
Molding;BIOMEDICAL ENGINEERING - Patient
Treatment;},
Abstract = {Polyanhydrides based on a variety of aromatic and aliphatic
dicarboxylic acids were developed as bioerodible carrier
matrices for controlled delivery applications. The high
hydrolytic reactivity of the anhydride linkage provides an
intrinsic advantage over other classes of bioerodible
polymers in versatility and control of degradation rates.
The polymers were characterized by infrared (IR),
differential scanning calorimetry, gel permeation
chromatography, and scanning electron microscopy (SEM). Near
zero-order degradation kinetics were observed for the
hydrophobic polyanhydrides over several months. Close
correlation of polymer degradation and drug release was also
observed in other injection-molded samples (10% loading),
suggesting a release mechanism that was dominantly
degradation controlled. Degradation of these polyanhydrides
was pH sensitive, being enhanced in high pH, and became more
stable in acidic conditions.},
Key = {85110160759}
}
@article{Article,
Author = {Leong, K. W. and Brott, B. C. and Langer,
R.},
Title = {Bioerodible Polyanhydrides as Drug-Carrier Matrices .1.
Characterization, Degradation, and Release
Characteristics},
Journal = {Journal of Biomedical Materials Research},
Volume = {19},
Number = {8},
Pages = {941-955},
Year = {1985},
Key = {Article}
}
@article{Article,
Author = {Langer, R. and Siegel, R. and Brown, L. and Leong, K. and Kost, J. and Edelman, E.},
Title = {Controlled Release and Magnetically Modulated Systems for
Macromolecular Drugs},
Journal = {Annals of the New York Academy of Sciences},
Volume = {446},
Pages = {1-13},
Year = {1985},
Key = {Article}
}
@article{84060106635,
Author = {Leong, K. W. and Brott, B. C. and Langer,
R.},
Title = {BIOERODIBLE POLYANHYDRIDES AS A DRUG CARRIER
MATRIX.},
Journal = {Polymer Preprints, Division of Polymer Chemistry, American
Chemical Society},
Volume = {25},
Number = {1},
Pages = {201 - 202},
Address = {St Louis, MO, USA},
Year = {1984},
Keywords = {POLYMERS;},
Key = {84060106635}
}
@article{Article,
Author = {Leong, K. and Forsman, W. C. and Vogel, F.
L.},
Title = {Conversion of Carbon Graphite Fibers to Fibers of Graphite
Oxide},
Journal = {Materials Science and Engineering},
Volume = {64},
Number = {2},
Pages = {149-155},
Year = {1984},
Key = {Article}
}
@article{Article,
Author = {Leong, K. and Forsman, W. C.},
Title = {Electron-Transfer to Protons in Graphite-Intercalation},
Journal = {Synthetic Metals},
Volume = {6},
Number = {1},
Pages = {61-63},
Year = {1983},
Key = {Article}
}
@article{Article,
Author = {Leong, K. and Tome, A. and Dziemianowicz, T. and Forsman,
W.},
Title = {Intercalation of Transition-Metal Dichlorides with No as
Coreagent},
Journal = {Synthetic Metals},
Volume = {7},
Number = {1-2},
Pages = {141-141},
Year = {1983},
Key = {Article}
}
@article{Article,
Author = {Forsman, W. C. and Dziemianowicz, T. and Leong, K. and Carl,
D.},
Title = {Graphite-Intercalation Chemistry - an Interpretive
Review},
Journal = {Synthetic Metals},
Volume = {5},
Number = {2},
Pages = {77-100},
Year = {1983},
Key = {Article}
}
@article{Article,
Author = {Leong, K. and Forsman, W. C. and Vogel, F.
L.},
Title = {Intercalation of Graphite with the Adducts of Nitrosyl
Chloride and Metal Chlorides},
Journal = {Carbon},
Volume = {20},
Number = {2},
Pages = {135-135},
Year = {1982},
Key = {Article}
}
@article{Article,
Author = {Leong, K. and Forsman, W. C.},
Title = {Vapor-Phase Intercalation by Alcl3-Hcl Mixtures},
Journal = {Carbon},
Volume = {20},
Number = {2},
Pages = {132-132},
Year = {1982},
Key = {Article}
}
@article{8589831,
Author = {Yim, E.K.F. and Reano, R.M. and Pang, S.W. and Yee, A.F. and Chen, C.S. and Leong, K.W.},
Title = {Nanopattern-induced changes in morphology and motility of
smooth muscle cells},
Journal = {Biomaterials (UK)},
Volume = {26},
Number = {26},
Pages = {5405 - 13},
url = {http://dx.doi.org/10.1016/j.biomaterials.2005.01.058},
Keywords = {biomechanics;biomedical materials;blood vessels;cellular
biophysics;muscle;nanopatterning;polymers;},
Abstract = {Cells are known to be surrounded by nanoscale topography in
their natural extracellular environment. The cell behavior,
including morphology, proliferation, and motility of bovine
pulmonary artery smooth muscle cells (SMC) were studied on
poly(methyl methacrylate) (PMMA) and poly(dimethylsiloxane)
(PDMS) surfaces comprising nanopatterned gratings with 350nm
linewidth, 700nm pitch, and 350nm depth. More than 90% of
the cells aligned to the gratings, and were significantly
elongated compared to the SMC cultured on non-patterned
surfaces. The nuclei were also elongated and aligned.
Proliferation of the cells was significantly reduced on the
nanopatterned surfaces. The polarization of microtubule
organizing centers (MTOC), which are associated with cell
migration, of SMC cultured on nanopatterned surfaces showed
a preference towards the axis of cell alignment in an in
vitro wound healing assay. In contrast, the MTOC of SMC on
non-patterned surfaces preferentially polarized towards the
wound edge. It is proposed that this nanoimprinting
technology will provide a valuable platform for studies in
cell-substrate interactions and for development of medical
devices with nanoscale features. [All rights reserved
Elsevier]},
Key = {8589831}
}
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