In Situ H2S-Releasing Stents Optimize Vascular Healing

Abstract

Stent implantation remains a cornerstone of interventional cardiology, providing a minimally invasive solution to restore blood flow in occluded vessels. However, current stents face persistent challenges in simultaneously preventing neointimal hyperplasia and promoting reendothelialization, compromising their long-term efficacy. To address these limitations, we developed an in situ H₂S-releasing polymer brush-coated stent that actively modulates material–blood interactions, creating a favorable microenvironment for vascular healing. H₂S enhances the stent’s antithrombotic properties by inhibiting fibrinogen binding and platelet activation, while also mitigating oxidative stress and promoting macrophage polarization toward the anti-inflammatory M2 phenotype. In vivo, the H₂S-releasing stents significantly improved vascular healing by accelerating endothelialization and inhibiting smooth muscle cell overproliferation, resulting in a thinner neointima with functional endothelial coverage. Transcriptomic analysis further elucidated the underlying mechanisms, revealing H₂S-mediated modulation of key biological pathways that support vascular healing. These findings underscore the potential of in situ H₂S release as an effective strategy for optimizing vascular implants and improving long-term outcomes.