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Forming porous structures is
useful in many applications including tissue regeneration, and
three-dimensional cell cultures. An important requirement is promoting
biological activity. Porous structures generated from natural and synthetic
polymers or after removing the cellular components from xenogeneic tissues
have been used to support and guide the in-growth of cells. A majority of
the clinical success in tissue regeneration has been accomplished using
substitutes derived from various tissues such skin, arteries, veins, or
xenogeneic sources. Examples include small intestinal submucosa (SIS),
acellular dermis or porcine pericardium. SIS is unique from other acellular
matrices as it contains growth factors. While using naturally formed
structures one concern is heterogeneity in source (microstructure of SIS
from different regions are shown below) and physicochemical characteristics.
Hence, manufacturing porous templates using pure components allows formation
of matrices with required features in addition to large scale production. |
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Scaffolds have been generated from synthetic and
natural polymers using various techniques such
as controlled rate freezing and lyophilization,
porogen-leaching technique, free-form printing
and electrospraying. Each technique has
advantages and disadvantages and many not be
suitable for all polymers. In addition,
developing porous structures using pure
components may not be useful as these pure
components do not recreate all the necessary
functionalities such as regulation on cellular
activity, weak mechanical strength and
inadequate tailorability to alter mechanical and
degradation properties. Combining two different
polymers is an attractive option to take
advantage of their positive characteristics and
wealth of previous literature. A significant
challenge in combining different polymers is the
chemistry of the two systems. For example, PLGA
(or PCL) is typically dissolved in halogenated
hydrocarbons (chloroform, methylene chloride,
etc) which are hydrophobic and sparingly
miscible in acidic water, the solvent used for
dissolving natural polymers. Chemically bonding
natural polymers (a classical example is heparin
conjugation) to other substrate results in loss
of bioregulation. |
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The overall goal of this project is to develop
technologies that produce three dimensional
porous matrices with well controlled and defined
features, useful in large scale regeneration of
tissues. Our group focuses on innovative methods
of dispersing the two polymeric systems without
chemically conjugating them with complex
reaction mechanisms. We work on generating
scaffolds from blends of natural and synthetic
polymers, based on the designed characteristics
of natural matrixes which have shown some
clinical success. Controlled rate freezing and
lypohilization (shown in the figure below)
technique is the method of choice while forming
scaffolds from natural polymers such as chitosan
and collagen, which dissolve in acidic water. |
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An additional method is electrospraying, a
widely established polymer processing technology
which allows generation of fibers in nanometer
to micrometer size, similar to that found in the
body. We have formed a) emulsion systems, b)
physically forcing synthetic and natural
polymers to co-exist, c) developing a unique
solvent mixture that can dissolve both natural
polymers (gelatin, chitosan, or collagen) and
synthetic PCL, or d) forming reinforced
composite systems. The composite matrix consists
of two porous compartments of natural polymers (chitosan/gelatin)
reinforced with a thin membrane of synthetic
polymers (PLGA or PCL). These approaches
inherently possess easy tailorability of
mechanical properties, permeability, pore size,
degradation characteristics, and biological
activity. We also work on delivering growth
factors using nanoparticles (shown in the figure
below) to create a heterogeneous environment
that could support the differentiation of stem
cells into needed cell types. We perform a wide
variety of mechanical testing analyses including
tensile, compression, cyclical, stress
relaxation testing under physiological
conditions and evaluate various mechanical
properties. These properties are compared with
natural tissues to assess their use. We also
model the mechanical behavior using concepts
developed in biomechanics such as the
viscoelastic behavior using quasi linear
viscoelastic models or various combination of
spring and dashpots using a proprietary code
developed by Dr. R Russell Rhinehart (Chem
Engineering, Oklahoma State University) in MS
Exel. |
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