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Research Projects |
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Immunomodulatory coatings for cell transplantation |
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This project is focused on the development of a novel type of
multifunctional cytoprotective material for coating living
pancreatic islets. Though transplantation of pancreatic islet
cells has emerged as a promising treatment for Type 1 diabetes,
its clinical application remains limited due to a number of
limitations including both pathogenic innate and adaptive immune
responses. The coatings being designed and developed in our
laboratory utilize hydrogen-bonded interactions of a natural
polyphenol (tannic acid) with poly(N-vinylpyrrolidone) or
poly(N-vinylcaprolactam) deposited on the islet surfaces via
nonionic layer-by-layer assembly. The developed material
combines high chemical stability under physiological conditions
with capability of suppressing cytokine synthesis, crucial
parameters for prolonged islet integrity, viability, and
function in vivo. This type of ultrathin multilayer coating
offers new opportunities in the area of advanced multifunctional
materials to be used for a cell-based transplantation therapy. |
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Surface multilayer hydrogels |
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This project examines the internal
architectures of pH- and temperature- responsive multilayer
hydrogels through the exploration of the stratification of
polymer layers within the matrices.
Thin surface-attached
multilayer hydrogels of stimuli-responsive polymers are
attractive candidates for applications in sensing, actuation,
and controlled delivery.
We
are developing novel synthetic assembly strategies with special
emphasis on nanostructured stimuli-responsive ultrathin
hydrogels.
The hydrogels are produced in
a stepwise assembly of polymers at surfaces.
The effects of cross-linking
paths, polymer molecular weight, chemical composition, and pH-
and temperature-triggered volume changes on hydrogel
architectures are examined.
The project requires
comprehensive analyses using unique in situ experimental
techniques: structural investigations with neutron
reflectometry, compositional analyses with ATR-FTIR, evolution
of swelling with in situ ellipsometry, and studies of hydrogel
morphology with AFM. |
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Stimuli-responsive shape transitions in multilayer
hydrogel capsules |
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In this project, a new class of
shape-changing materials based on ultrathin hollow
microparticles (capsules) of specific shape is being developed.
The capsule wall is comprised
of a stimuli-sensitive polyelectrolyte hydrogel and is formed
using a multilayer approach. The capsules are being designed to
reversibly change geometry in response to environmental stimuli
(pH, T) with the shape-switchable mechanism controlled at the
molecular level. Two types of pH-triggered shape response in
cubical hollow microcapsules have been developed. The cubical
microcontainers are produced as hydrogel replicas of cubical
inorganic microparticles by chemically cross-linking multilayers
of hydrogen-bonded coatings.
While cubical single-component
capsules turn into spherical-like when transitioned from acidic
to neutral pH, cubical two-component hydrogel capsules retain
their cubical shape and increased in size. |
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Thermosensitive multilayer hydrogel
films and capsules with a distinct and highly reversible
thermoresponsive behavior have also been developed. The cubical
temperature-responsive hydrogel capsules shrink upon temperature
increase while retaining their cubical shape. The hydrogels are
derived from hydrogen-bonded multilayers through chemical
cross-linking of the copolymer layers.
The degree of hydrogel
temperature-triggered shrinkage can be controlled by varying the
cross-link density by ranging the amount of cross-linkable
groups in the copolymer chains. Since the dynamic control over
materials shape plays a key role in the complex biological
environment and is important in engineering science and
medicine, the project findings can provide new prospects for
developing polymeric materials with predictable shape and
size-changing properties for controlled delivery and
shape-regulated cellular uptake. |
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Nanocapsule carriers for ultrasound-induced local
delivery |
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The major focus of this research is
to develop novel polymer-based nanostructured carriers for
delivery of anticancer drugs using ultrasound for targeting
delivery. Oncology is a field of medicine for which there has
been a remarkable contribution from nanotechnology. One of the
most challenging problems still remains unresolved is controlled
delivery of therapeutics to solid tumors. The project focuses on
development of approaches for encapsulating anticancer drugs or
viral agents within microcapsule carriers for controlled
delivery to tumors. Biocompatible and biodegradable
microcapsules consisting of open submicron-size cavity and
ultrathin polymeric shell are being synthesized and utilized as
carriers.
The release efficacy is
assessed in cancer cell cultures using microscopy and flow
cytometry. Left: CLSM and SEM images of DOX-loaded capsules. |
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Multilayer capsules for shape-controlled cellular uptake |
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This project focuses on the
development of the multilayer micro- and nanocapsules
(nanovectors) of non-spherical shape for controlled cellular
uptake.
In nature, each shape evolved
for specific physiological reasons. Non-spherical shape and
elasticity are the physical characteristics responsible for
ability of cells to overcome transport barriers en route to the
target lesion, which are universal for cells transported in the
blood stream. The shape of erythrocytes guarantees the optimal
surface-to-volume ratio that is necessary for margination in the
blood and enabling the delivery of oxygen from hemoglobin to the
outside tissues. The extraordinary flexibility of mammalian
erythrocytes enables them to deform in the circulation as they
pass through restrictions in the vasculature that is smaller
than their diameter. We design cell-mimicking nanovectors
possessing the characteristics of elasticity and responsiveness
to pH gradients in tumor microenvironment. The layer-by-layer
assembly of biocompatible and pH- sensitive polymers is used to
produce capsules with cell-mimicking shapes.
The effect of capsule shape
and elasticity on the interaction with cells present in the
circulation and tumor microenvironment are being explored in
comparison to their rigid counterparts.
Left: Confocal laser scanning
microscopy images of hollow shaped polymer capsules of silk
fibroin protein LbL-assembled with polyvinylcaprolactam via
hydrogen bonding.
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