Date of Award

Spring 1-1-2013

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Mechanical Engineering

First Advisor

Wei Tan

Second Advisor

Virginia Ferguson

Third Advisor

Stephanie Bryant

Fourth Advisor

Yifu Ding

Fifth Advisor

Raphael Nemenoff

Abstract

Cardiovascular diseases are the leading cause of death in the western world. Regeneration of functional vascular tissue remains a critical barrier to successful treatment of these diseases. Attempts to produce functional vascular tissue with autogenous vascular cells have limited success due to the need for invasive surgery. Mesenchymal stem cells (MSCs) are a powerful cellular alternative for vascular regeneration as they are easily obtainable, multipotent, and thrombo-resistant. Currently, the mechanisms that drive MSC differentiation to healthy or diseased vascular phenotypes are not well understood. There is a critical need to define the factors in the cellular microenvironment that guide MSC differentiation. This dissertation examines how matrix elasticity, composition, and exogenous chemicals interact to direct the vascular differentiation of MSC. Polymer nanofiber matrices are fabricated with tunable elasticity utilizing electrospinning and photopolymerization techniques. Varying the elasticity of the matrix directs MSC differentiation towards either endothelial or smooth muscle cell lineage, while the addition of exogenous chemicals furthers MSC differentiation to mature vascular phenotypes. The incorporation of peptides in these matrices increases MSC adhesion and proliferation. This dissertation highlights the importance of carefully modulating both chemical and mechanical factors when designing cell therapies or tissue engineered grafts for vascular tissue regeneration.

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