Date of Award

8-2016

Document Type

Thesis

Degree Name

Master of Science (MS)

Legacy Department

Bioengineering

Committee Member

Dr. Ken Webb, Committee Chair

Committee Member

Dr. Scott Taylor

Committee Member

Dr. Jiro Nagatomi

Abstract

For patients with organ failure complications, organ transplantation is not alwaysan option due to a shortage of donors along with obstacles such as risk of pathogentransfer and the possibility of immune rejection. Tissue engineering approaches based oncell therapy provide a promising alternative that could potentially solve these problems.The success of cell therapy for tissue repair and regeneration requires reliable andefficient cell delivery methods. Currently, hydrogels are favored matrices for celldelivery because of their ability to be injected by minimally invasive techniques asviscous liquids and crosslinked in situ under mild conditions compatible with thehomogeneous incorporation of cells and bioactive molecules. However, hydrogels haveseveral limitations including relatively weak mechanical properties that limit cellproliferation and allow premature contraction, as well as their hydrophilic compositionthat offers little capacity for binding secreted extracellular matrix (ECM) molecules tosupport higher order assembly. The long-term objective of this research is to develop acomposite cell delivery matrix composed of a biosynthetic hydrogel containing porous,hydrophobic microparticles. Toward this end, the project examined optimization ofprocessing variables to create porous Strataprene® 3534 polymer microspheres,examined their concentration-dependent effects on hydrogel physicochemical properties,and evaluated their ability to support cell adhesion. By decreasing polymer andincreasing porogen concentrations, particles with increased porosity were attained.Hydrogel/particle composites maintained mechanical integrity with modest decreases ingelation efficiency and elastic modulus relative to hydrogel-only controls. Strataprene® 3534 polymer films supported robust cell adhesion and spreading approximating tissue culture plastic controls and substantially greater than poly (lactide-co-glycolide) films. Cell adhesion to microparticles was less efficient, perhaps due to entrapment of poly(vinyl alcohol) used to stabilize the secondary emulsion on the surface of the microparticles. Overall, these studies demonstrate that highly porous polymer microparticles can be achieved and successfully incorporated into hydrogels to create composites without substantially altering the gel’s physical properties. Future studies will examine improvement of cell adhesion and composite functionality for enhancing cell proliferation and ECM accumulation.

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