One Produces Multi: A Drug-free Cardiovascular Stent Functionalized with Tailored Collagen Supports in-situ Healing of Vascular Tissues

Abstract Drug-eluting stent implantation suppresses the proliferation of vascular endothelial cells and smooth muscle cells and thus intimal hyperplasia. However, drug-eluting stent remains limited by delayed reendothelialization, impaired intimal remodeling, and potentially increased late restenosis. Here, we show a drug-free coating formulation functionalized with meticulously tailored recombinant humanized collagen type III (rhCol III) that performs “one produces multi” behavior in response to injured tissue following stent implantation. In vitro and in vivo experiments have demonstrated that the “one produces multi” coating has the properties of resisting coagulation, reducing inflammatory responses by regulating macrophage polarization, and inhibiting the proliferation of smooth muscle cells. Furthermore, the drug-free coating accelerated neointimal healing probably via cell signaling of CCL5, CEACAM6, GATA3, and XBP, which influences the cell adhesion, proliferation, migration, and apoptosis pathways. Compared with drug-eluting stent, the rhCOL III-coated stent reduced in-stent restenosis and improved vascular neointimal healing 3 months after implantation in both rabbit and porcine models. Collectively, the “one produces multi” drug-free strategy has the potential to serve as a new inspiration for next-generation stent development.