Microenvironment-responsive magnesium stents for targeted atherosclerotic plaque removal and restenosis mitigation.

Abstract

Atherosclerotic plaque persistence and maladaptive vascular remodeling drive in-stent restenosis despite effective revascularization. Here, we develop a microenvironment-responsive magnesium stent with an EGCG-Cys-MFVL nanocoating for targeted plaque clearance. The system enables cholesterol oxidation, reactive oxygen species (ROS) scavenging, and targeted delivery, reprogramming macrophage polarization and vascular homeostasis. Mechanistically, it activates PPARγ/PGC1α pathways in endothelial cells while suppressing proliferative signaling in smooth muscle cells. In vivo, the stent exhibits enhanced plaque targeting, prolonged retention, and sustained efficacy, reducing neointimal hyperplasia and improving luminal patency across multiple animal models. Long-term evaluation shows favorable biosafety and degradation. These findings establish a device-integrated strategy for coordinated plaque removal and microenvironmental remodeling to mitigate restenosis.