Microenvironment-responsive coating for vascular stents to regulate coagulation-inflammation interaction and promote vascular recovery

Abstract

Early coagulation-inflammation interaction and late in-stent restenosis undermine the efficacy of vascular stents after implantation. Targeting the interplay between inflammation and coagulation, and smooth muscle cell (SMC) proliferation, we presented a microenvironment-responsive coating designed to regulate tissue responses and vascular regeneration throughout the remodeling process. Coagulation was inhibited by incorporating anticoagulant tirofiban into the coating. MMP9-responsive nanoparticles embedded in the coating released salvianolic acid A to modulate inflammatory cell behavior and inhibit SMC dysfunction. By effectively interfering with clotting and inflammation, the coating suppressed platelet-fibrin interaction and formation of platelet-monocyte aggregates, thereby mitigating adverse effects on reendothelialization. Its ability to influence SMC proliferation and migration resulted in reduced intimal hyperplasia. Coated stents were shown to significantly regulate tissue regeneration, improve the vascular environment and even reduced the lipid content in the narrowed atherosclerotic vessels in vivo. This direct approach enhanced the vascular tissue regeneration after stent implantation, and offered promising insights for optimizing vascular stent design.