Date of Award

12-15-2014

Document Type

Open Access Dissertation

Department

Biomedical Engineering

First Advisor

Tarek Shazly

Abstract

Background: Implantation of vascular grafts provides a means to restore blood flow in compromised regions of the circulatory system, and thus is used to treat a wide range of cardiovascular diseases. Despite significant advancements in autologous grafting strategies as well as the engineering of synthetic alternatives, mechanical, structural, and compositional incongruities between the graft and the host artery remain as contributing factors to graft failure. The typical failure modality manifests as proximal anastomotic intimal hyperplasia, which places restrictions on the host vessel size currently treated with grafting strategies (> 5 mm internal diameter). In order to improve long-term clinical outcomes, this project is devoted to experimental investigations of native and engineered vascular mechanics, with development of structure-motivated constitutive models that promote both the optimal selection of native vascular grafts and fabrication of engineered vascular substitutes.

Dissertation summary: The overall goal of this project is to characterize and model the mechanical properties of native arteries, with focus on the primary renal artery, as well as a representative material for the engineering vascular substitutes. In our first set of studies, we employed an integrated experimental-theoretical methodology to study the passive mechanical behavior of porcine primary renal artery. Inflation-extension tests and structure-motivated constitutive models were used to characterize the contribution of structural constituents, such as elastin and collagen, to the macroscopic mechanical response of the arterial wall. In our next set of studies, we sought to understand how vascular smooth muscle cell contractile states modulate the mechanical responses of arterial wall. Active stresses induced by vascular smooth muscle cell contraction were derived via isometric contraction studies, and analytical expressions to characterize the biaxial active stress-strain relationships were proposed. Thirdly, for the sake of appropriate selection of an autologous source for coronary artery end-to-end grafting, the passive mechanical behaviors of porcine coronary artery, internal thoracic artery, radial artery, great and lateral saphenous veins were assessed and compared. Differences in compliance, average wall stresses, and deformed inner radii between the coronary artery and the graft were proposed as a basis for optimal tissue selection and implantation strategy. Finally, the mechanical properties of novel engineered vascular constructs were characterized as a function of fabrication protocol. The mechanical response of tissueengineered constructs, and more specifically the compositional determinants of exhibited behavior, indicates these materials could be further developed for grafting applications. Taken together, the studies encompassed in this dissertation provide a comprehensive framework to improve the clinical implementation of autologous vascular grafts and direct the engineering of vascular substitutes.

Rights

© 2014, Boran Zhou

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