Bioinspired ECM-mimetic peptide nanofibrous coatings promote re-endothelialization on vascular stents.

Cardiovascular stents are life-saving interventions for occlusive vascular diseases, yet current designs such as drug-eluting stents suppress restenosis via universal antiproliferation, inevitably impairing endothelial regeneration and raising the risk of late thrombosis. Here, we introduce a bioinspired endothelial-selective peptide self-assembling nanofibrous coating (ECSP-SANC) that integrates extracellular matrix (ECM)-mimetic β-sheet nanofibrous topography with REDV (Arg-Glu-Asp-Val)-mediated endothelial recognition cues to create a regenerative stent interface. ECSP-SANC forms a highly hydrated three-dimensional nanofibrous network that recapitulates key architectural features of native ECM while displaying accessible REDV motifs to preferentially promote endothelial cell adhesion, migration, proliferation, and functional maturation. In parallel, the coating suppresses smooth muscle cell overgrowth and synthetic phenotypic switching, thereby conferring an endothelial competitive advantage on the stent surface. The hydrated nanofibrous interface also minimizes platelet adhesion and inflammatory responses, contributing to improved hemocompatibility and local immune regulation. In a rabbit iliac artery implantation model, ECSP-SANC-functionalized stents accelerated re-endothelialization, suppressed neointimal hyperplasia, and effectively prevented restenosis. This approach demonstrates that precise integration of endothelial-selective biochemical signals with ECM-mimetic architecture can orchestrate vascular repair beyond conventional antiproliferative strategies. ECSP-SANC represents a versatile, next-generation platform for regenerative stent coatings, offering a blueprint for cardiovascular therapies that harmonize anti-restenotic efficacy with rapid endothelial recovery.