Access Type

Open Access Dissertation

Date of Award

1-1-2010

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Chemical Engineering and Materials Science

First Advisor

Howard Matthew

Abstract

DESIGN OF A POLYSACCHARIDE DERIVED TISSUE ENGINEERED VASCULAR GRAFT

By

Irina Robu

November 2010

Advisor: Dr. Howard Matthew

Major: Chemical Engineering

Degree: Doctor of Philosophy

As the most frequent congenital anomaly and the leading cause of death, congenital heart disease is an attractive target for tissue engineering research. The challenging target to engineer a native blood vessel stems from the need to find substitutes for pediatric patients born with congenital defects. The tissue engineering graft functions to bring various cells of the vasculature in close proximity to one another to enable intercellular signaling which facilitates cell adhesion, migration and differentiation.

Our long-term objective is to fabricate a polysaccharide based vascular graft based on the use of chitosan, for the development of a large vascular graft for pediatric applications. Chitosan is biodegradable, biocompatible and biologically active which would not spawn any detrimental inflammatory responses.

In this work, we compared the effects of glycosaminoglycans (GAG) and a GAG-like polyanion as modifiers of smooth muscle and endothelial cells activity. We also investigated various scaffold formulations and seeding techniques for enhanced cellular entrapment and high cell proliferation. In-vitro, 3D scaffold cultures under non-pulsatile and pulsatile flow conditions were explored to generate vascular grafts with appropriate cellular alignment and tissue generation.

We explored the prospect of a tissue engineered large vessel graft using polysaccharide biomaterials, which would be conditioned in a 3D environment similar to the physiological conditions.

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