Date of Award

2014

Document Type

Open Access Dissertation

Department

Biomedical Engineering

First Advisor

Tarek Shazly

Abstract

Background: Bioresorbable scaffolds (BRS) have revolutionized percutaneous coronary intervention in clinical cardiovascular medicine. As opposed to permanent alternatives such as metallic stents, BRS have an inherent potential to reduce the occurrence of untoward events such as vessel re-narrowing or thrombosis by virtue of undergoing complete and controlled resorption post- implantation. While BRS platforms demonstrate a clear potential to mitigate risk stemming from incomplete vessel healing, they introduce a new set of considerations to clinical safety and efficacy. Foremost among these issues is the fate of and biological response to material by-products that evolve throughout the scaffold degradation and erosion processes, motivating a comprehensive assessment of how material design and deployment parameters impact scaffold performance in the arterial environment.

Dissertation summary: The overall goal of this project is to identify performance criteria of BRS for endovascular applications. First, we develop a computational model to predict scaffold by-product generation and release throughout the tissue healing process. Parametric studies are used to elucidate the material and deployment parameters which most significantly modulate by-product fate and thus patient risk. We next perform an array of in vitro studies to understand how BRS fracture risk depends on the expansion ratio imparted at implantation. Due to the inherent potential for fracture during endovascular delivery, BRS over expansion is a more serious concern as compared to analogous deployment of metallic stents. Conversely, under expansion increases the risk of thrombosis due to an alteration of in situ geometry and concomitant disturbance of arterial blood flow. To gain insight on the effects of scaffold expansion, computational studies are complemented by in vitro measures of BRS erosion, degradation, radial strength, and drug delivery kinetics under plausible alterations of the degree of expansion. Finally, a dynamic flow system which mimics arterial blood flows is developed and used to study the effects of the specific implantation site on BRS performance. Taken together, the studies encompassed in this dissertation provide an efficient means for iterative evaluation of candidate scaffolds as well as the basis to optimize material design and delivery strategies as this technology continues to evolve.

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