All ETDs from UAB

Advisory Committee Chair

Yogesh Vohra

Advisory Committee Members

Alan Eberhardt

Steven Pogwizd

Raj Singh

Vinoy Thomas

Document Type

Dissertation

Date of Award

2015

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

Atherosclerosis is an asymmetric thickening of the intima (innermost layer) of the artery due to plaque (a combination of lipids, debris, connective tissue elements and cells) build up causing the artery to become narrower and stiffer, resulting in a major hemodynamic disturbance[1, 2]. When atherosclerosis affects coronary arteries and prevents blood flow to the heart muscles posing a threat of, or a actual myocardial infarction, that condition is identified as coronary artery disease (CAD). To treat severely blocked coronary arteries,coronary artery bypass grafts (CABG) have became the gold standard for when angioplasty and stent placement has failed to unclog the artery. However, there are significant limitations associated with the CABG procedure. First, these autologous grafts are not available in 20-30% of patients due to peripheral vascular disease[3]. Second, the site from which the autologous artery is removed may become ischemic[4]. Third, veins show poor performance at high pressure artery sites due to fundamentally different mechanical properties compared to arteries. These varying mechanical problems can cause compliance mismatch leading to an aneurysm, intimal hyperplasia or atherosclerosis in the long run[5]. Fourth, repeated surgery is generally needed within 10 years due to a significant reduction in the patency of these autologous grafts [6]. As an alternative strategy, synthetic and non-degradable vascular grafts have been used to overcome the limitations of autologous grafts; however, stenosis, thromboembolization, intimal hyperplasia, hemodynamic disturbances, and infection can became significant issues due to lack of endothelial cells on the lumen layer [7, 8] due to the mismatch of mechanical properties . Therefore, there is a unmet need for an ideal vascular graft that is mechanically strong, non-immunogenic, non-toxic, is resistant to thrombosis, promotes regeneration and can withstand long term hemodynamic stresses, [8, 9]. An ideal vascular graft should be able to maintain function identical to or reminiscent of a native artery directly after implantation and resorb at a rate coinciding withsatisfactory regeneration of the neo vascular tissue. The goal of this study is to engineer and evaluate a bio-hybrid vascular graft and evaluate its mechanical properties as well as biocompatibility with endothelial cells (ECs) and smooth muscle cells (SMCs) to serve as a potential treatment option for CAD. This assembly which closely mimics the native coronary artery structure will be engineered via an electrospinning technique. The bio-hybrid graft is made of biocompatible, biodegradable, and resorbable synthetic polymers such as polycaprolactone (PCL), poliglecaprone (PGC), and a natural human derived biomatrix dubbed HuBiogelTM designed to mimic the extracellular matrix (ECM) of blood vessels. To better enhance endothelialization and reduce thrombosis, the bio-hybrid graft has been designed so that a greater concentration of the unique human derived biomatrix is deposited on the outer layer with a lower concentration deposited on the inner lumen.

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