Hao Xu

Graduation Semester and Year

2010

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Biomedical Engineering

Department

Bioengineering

First Advisor

Liping Tang

Abstract

Current synthetic vascular grafts and polymer-coated drug-eluting stents (DES) have certain limitations, such as thrombosis and restenosis due to the incomplete recovery of vascular endothelial cells on their luminal sides. Surface modification of these materials is a viable method to enhance the endothelialization on them. In this study, we proposed several way to modify poly(L-lactic acid) (PLLA), a promising material for vascular prostheses to enhance the endothelialization on its surface. In the first method, we modified the material surface with deposition of poly(vinylacetic acid) (PVAA) using plasma polymerization. PVAA having different surface densities of -COOH group or film thickness were created and characterized. Their effects on endothelial cell adhesion, proliferation, and function were tested. PVAA films with 9% -COOH surface density and 100 nm film thickness were found to be optimal for enhancing endothelialization. The mechanism might involve the increased fibronectin adsorption on its surface. In the second method, fibronectin was conjugated covalently with PVAA, which was deposited on PLLA, utilizing the rich -COOH of PVAA. Vascular Endothelial Growth Factor (VEGF) was subsequently conjugated with FIBRONECTIN for a controlled release. Enhanced endothelial cells adhesion and proliferation was found on this modified PLLA surface, with well preserved endothelial cell function. Lastly, we coated PLLA with poly(1,8-octanediol-co-citrate) (POC) / poly(lactic-co-glycolic acid) (PLGA) microparticle composite. Growth factors VEGF and fibroblast growth factor (FGF), and VEGF Receptor plasmids were encapsulated in the PLGA microparticles for controlled delivery. Fibronectin and anti-CD34 antibody were, in turn, conjugated on top of POC to capture endothelial progenitor cells (EPC). It was found that the surface modified PLLA successfully captured EPCs in a flowing condition, and rendered quick endothelialization on the surface. Using these strategies, enhanced endothelialization can be achieved on polymers, which naturally do not support endothelial cell growth, such as PLLA in order to reduce thrombosis and restenosis on vascular prostheses.

Disciplines

Biomedical Engineering and Bioengineering | Engineering

Comments

Degree granted by The University of Texas at Arlington

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