Perivascular CLICK‐gelatin delivery of thrombospondin‐2 small interfering RNA decreases development of intimal hyperplasia after arterial injury

Abstract

Bypass graft failure occurs in 20%–50% of coronary and lower extremity bypasses within the first‐year due to intimal hyperplasia (IH). TSP‐2 is a key regulatory protein that has been implicated in the development of IH following vessel injury. In this study, we developed a biodegradable CLICK‐chemistry gelatin‐based hydrogel to achieve sustained perivascular delivery of TSP‐2 siRNA to rat carotid arteries following endothelial denudation injury. At 21 days, perivascular application of TSP‐2 siRNA embedded hydrogels significantly downregulated TSP‐2 gene expression, cellular proliferation, as well as other associated mediators of IH including MMP‐9 and VEGF‐R2, ultimately resulting in a significant decrease in IH. Our data illustrates the ability of perivascular CLICK‐gelatin delivery of TSP‐2 siRNA to mitigate IH following arterial injury.