All ETDs from UAB

Advisory Committee Chair

Ho-Wook Jun

Advisory Committee Members

Brigitta C Brott

Derrick R Dean

John C Middleton

Young-Sup Yoon

Joel L Berry

Document Type

Dissertation

Date of Award

2013

Degree Name by School

Doctor of Philosophy (PhD) School of Engineering

Abstract

Bioinspired solutions for challenges faced by conventional therapies are rapidly emerging, especially as new and innovative improvements in medical devices are constantly being researched and developed. Stents are a common therapeutic device for cardiovascular diseases that have undergone incrementally developmental changes over the last two decades. However, there are concerns about in-stent restenosis with bare metal stents and incomplete endothelialization, late stent thrombosis, and late inflammatory responses with drug-eluting stents. New strategies for stents include the development of bioresorbable stents and the utilization of endothelial progenitor cell capture techniques. Despite the promise of recent developments aimed at overcoming the limitations of current stents, concerns still remain and success is limited. It is critical to develop an innovative strategy to overcome these limitations. Hence, the goal of this dissertation is to develop a bioinspired strategy for a multifunctional self-assembled peptide amphiphile (PA) nanomatrix coating that can provide characteristic properties of the native endothelium on the surface of stents. The PAs used in the study to develop an endothelium mimicking stent coating comprise endothelial cell adhesive ligands, nitric oxide donors, enzyme mediated degradable sites, and water based self-assembly into a nanofibrous matrix. Incorporation of these features endows the nanomatrix with the ability to closely mimic the native endothelium. It is hypothesized that this bioinspired multifunctional nanomatrix promotes endothelialization, but limits neointimal hyperplasia, restenosis, thrombosis, and inflammatory reactions. Preliminary studies have successfully demonstrated the feasibility of the bioinspired multifunctional nanomatrix. Successful self-assembly into nanofibers and long term release of nitric oxide was achieved. The bioinspired nanomatrix promotes endothelial proliferation, but limits smooth muscle cell proliferation and platelet adhesion. It also promoted the adhesion and differentiation of endothelial progenitor cells. This bioinspired multifunctional nanomatrix coating has the potential to overcome current challenges of stents and further be applied to various cardiovascular implants.

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Engineering Commons

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