A tough nitric oxide-eluting hydrogel coating suppresses neointimal hyperplasia on vascular stent

Yin Chen,Hua Qiu,Peng Gao,Hongkai Wu,Ningling Zhou,Qiufen Tu,Xin Dai,Sean Michael,Nan Huang,Jianhua Zhou,Xing Tan,Zhilu Yang,Tong Yang,Zhihong Guo,Lu Huang

doi:10.1038/s41467-021-27368-4

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. 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.

Highlights

Vascular stent is viewed as one of the greatest advancements in interventional cardiology
It seems the sol–gel transition of gelatin solution can be utilized for that purpose, which liquefies when the temperature is above the melting point (Tm) of gelatin and solidifies after cooling
We reported that Michael-addition reaction between amine and maleimide could be leveraged for crosslinking a hydrogel[20,21]

Summary

Introduction

Vascular stent is viewed as one of the greatest advancements in interventional cardiology. 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. Through conjugation of an organoselenium species to alginate, the hydrogel is capable of persistently catalyzing the generation of NO Such NOE hydrogel coating can withstand the balloon dilation during angioplasty, prevent thrombosis, inhibit the overgrowth of smooth muscles, promote the rapid restoration of native endothelium, and effectively suppress NIH on vascular stents

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Results

Conclusion