All ETDs from UAB

Advisory Committee Chair

Ho-Wook Jun

Advisory Committee Members

Brigitta C Brott

Jeong-A Kim

Palaniappan Sethu

Timothy M Wick

Document Type

Dissertation

Date of Award

2018

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

Cardiovascular disease is currently the number one cause of death in the United States, and indeed, worldwide. Stents are the most commonly implanted devices used to treat cardiovascular disease. Bare metal stent use remains limited by relatively high rates of in-stent restenosis, a re-narrowing of the artery after stent deployment. Restenosis within stents is a result of neointimal proliferation of smooth muscle cells and the accom-panying extracellular matrix deposition in response to vessel injury. To address this, drug-eluting stents have been developed to reduce restenosis; however, difficulties with late stent thrombosis, inflammation, and poor re-endothelialization remained. Thus, alt-hough numerous approaches have been investigated to overcome these challenges, development of innovative strategies to restore endothelium healing while limiting restenosis, thrombosis, and inflammation remains elusive. Therefore, in order to address the current clinical shortcomings of stents, we aimed to develop a novel prohealing multifunctional endothelium nanomatrix coating for stents, which can minimize the risks of late stent thrombosis, restenosis, inflammatory responses, and incomplete endothelialization, and can restore the healthy endothelium on the surface of stents. The inclusion of endothelial cell adhesive ligands, enzyme-mediated degradable sites, and nitric oxide donors provides native endothelium mimicking characteristics to the nanomatrix coated onto the stents, which can enhance stent efficacy by promoting endothelial healing on the surface of the stent. Due to the importance of inflammatory responses to foreign materials and stent coatings, we evaluated the effect of the novel prohealing multifunctional endothelium nanomatrix coating for stents on inflammation in vitro under both static and physiological flow conditions. We then determined the effect of the nanomatrix coated stents on endothelialization, smooth muscle cell migration, and inflammatory cell and platelet adhesion under physiological flow in vitro. Finally, we determined the efficacy of the nanomatrix coated stent in rat mesenteric arterioles ex vivo and in a rabbit iliac artery balloon injury model in vivo. This provides a paradigm changing approach: 1) a prohealing strategy through the synergistic effects of multiple bioactive functions, 2) endothelium-mimicking characteristics to limit restenosis and thrombosis, and 3) biocompatibility of peptide amphiphiles without organic solvents to reduce inflammation. Therefore, the prohealing multifunctional endothelium nanomatrix coating for stents can promote endothelial healing while limiting restenosis, thrombosis, and inflammation in order to enhance the efficacy of stents and address the clinical concerns of currently available cardiovascular stents.

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