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Durotaxis Directed Cell Migration for Enhanced Vascular Stent Endothelialization

Abstract

Vascular stents often cause adverse physiological responses as a result of inadequate endothelialcoverage. The new generation of vascular stent designs includes substratums with nanopatternedtopographies that enhance cell functionality for rapid endothelialization. Quick endothelializationcan be achieved by promoting cell migration rate and guiding cell migration direction, factorsaccomplishable by durotaxis, stiffness directed cell motility. However, the stiffness gradientrequired to induce durotaxis has not yet been implemented in materials viable for vascular stents.Our objective is to improve upon existing stent designs through durotaxis by studyingendothelial cell migration on biodegradable chitosan modified with nanopatternedtopography and gradated stiffness. We will fabricate three nanostructured substrates with 400nm pitch rectangular grooves and ridges possessing different stiffness gradients of 1 Pa/um, 10Pa/um, and 100 Pa/um and seed them with human umbilical vein and human aortic endothelialcells. We expect our nanostructured substrates will outperform our only topographicallymodified (no stiffness gradient) control and flat surface control. The proposed study will not onlyoffer a potential solution for improved endothelialization but also offer a proof of concept forintegration of durotaxis to vascular stent designs..

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