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The Washington Research Foundation Fellowship
Jun Park, Bioengineering, 2010-11 WRFF
It was my presentation assignment for my honors biology seminar class during my sophomore year when I first came across the current problem with stents. While preparing for the presentation, I realized that there are over 700,000 patients who undergo stent surgeries each year, but with 33% of those patients suffering from stent failures called in-stent restenosis. Despite the known shortcomings involved with stents, stent surgeries have become very popular as the benefits outweigh the risks: it really bothered me, and I thought something had to be done to address this problem. The summer after my freshman year, I joined the materials science lab of Professor Mehmet Sarikaya. Working in the lab for over 2 years, I gained much valuable skills and knowledge of genetically engineered peptides that bind to inorganic surfaces such as gold and titanium. Having investigated various aspects and applications of the inorganic binding peptides, I decided to tackle that medical challenge I came across few years ago. After graduation, I plan to pursue a MD-PhD degree, and I hope to contribute to the field of biomaterials during my career as a research scientist. I am thankful for the generous support provided by the Washington Research Foundation Fellowship as it allowed me to focus on my research and further motivated me to pursue a career in biomedical research.
Mentor: Mehmet Sarikaya, Materials Science and Engineering
Project Title: Accelerated Endothelialization of Stents by Titanium-Binding Peptide Conjugated with Integrin-Binding RGDS: Recruitment of endothelial progenitor cells and inhibition of neointimal hyperplasia
Abstract: Immobilization of endothelial progenitor cells (EPCs) on stent surfaces have previously been identified as a potential solution to solving the current problem with stents: in-stent restenosis, the re-narrowing of the blood vessels due to scar tissue formation around implanted stents. Despite the effective reduction of in-stent restenosis, current drug-eluting stents face various challenges including side effects involved with anti-inflammatory drug coatings, high risk of thrombosis and high costs. In this study, a novel bifunctional peptide with two binding motifs, one that can bind to a titanium oxide layer, TiBP, and the other that can bind to EPCs, RGDS, will be synthesized into a single peptide construct and utilized to create peptide-functionalized stents that can capture EPCs. The material specificity and self-assembling characteristics of the TiBP-RGD peptide will help immobilize circulating EPCs onto the stent surface, promoting neighboring endothelial cell proliferation and preventing scar tissue formation around the stent. In order to verify successful immobilization of EPCs on the stent surface, the targeting specificity and binding affinities of TiBP-RGD peptide toward metal stents and EPCs will be tested on commercially available stents, as well as stents coated with titanium or gold layers. EPC immobilization will be tested in vitro and ex vivo under lateral flow conditions. Cell immobilization will be verified using histomorphometric analysis, bright field microscopy of the extransplanted stents, surface plasmon resonance spectroscopy and high performance liquid chromatography to quantify peptide binding and cell detachment.