Vascular stent is viewed as one of the greatest advancements in interventional cardiology. However, current approved stents suffer from in-stent restenosis associated with neointimal hyperplasia or stent thrombosis. Herein, we develop a nitric oxide-eluting (NOE) hydrogel coating for vascular stents inspired by the biological functions of nitric oxide for cardiovascular system. Our NOE hydrogel is mechanically tough and could selectively facilitate the adhesion of endothelial cells. Besides, it is non-thrombotic and capable of inhibiting smooth muscle cells. Transcriptome analysis unravels the NOE hydrogel could modulate the inflammatory response and induce the relaxation of smooth muscle cells. In vivo study further demonstrates vascular stents coated with it promote rapid restoration of native endothelium, and persistently suppress inflammation and neointimal hyperplasia in both leporine and swine models. We expect such NOE hydrogel will open an avenue to the surface engineering of vascular implants for better clinical outcomes.

No abstract

Vascular stent is viewed as one of the greatest advancements in interventional cardiology. However, current approved stents suffer from in-stent restenosis associated with neointimal hyperplasia or stent thrombosis. To address this issue, we developed an endothelium-like (EL) dressing for vascular stents inspired by the importance and biological functions of native endothelium for cardiovascular system. Our EL dressing is based on a de novo designed hydrogel that is mechanically tough and could preserve integrity on stents during angioplasty. Due to its physiochemical similarities to subendothelial extracellular matrix, the EL dressing facilitated the adhesion and growth of endothelial cells. Besides, it is non-thrombotic and capable of inhibiting smooth muscle cells thanks to the capacity to catalyze nitric oxide generation. Transcriptome analysis further unraveled the EL dressing could modulate the inflammatory response and induce the relaxation of smooth muscle cells, while potentially promoting angiogenesis by stimulating the expression of angiogenic factors. In vivo study demonstrated vascular stents encapsulated by it promoted rapid restoration of native endothelium and persistently suppressed in-stent restenosis in both leporine and swine models. We expect such EL dressing will open a new avenue to the surface engineering of vascular implants for better clinical outcomes.