Copper sulfide nanozyme with antioxidative stress, anti-inflammation, and anti-calcification for vascular regeneration.

Small-diameter vascular grafts are inevitably subjected to oxidative stress and inflammatory responses, which delay graft endothelialization and ultimately result in intimal hyperplasia and vascular calcification. In this study, copper sulfide (CuS) nanozymes with catalase(CAT) and glutathione peroxidase(GPx) like activities were developed, which could simultaneously generate nitric oxide (NO) and hydrogen sulfide (H2S). CuS nanozymes were blended with polymer and electrospun to prepare grafts. The grafts could reduce reactive oxygen species levels, inhibit inflammatory responses, enhance endothelial cell function, while suppressing the excessive proliferation of smooth muscle cells. In addition, the grafts exhibited excellent biocompatibility, mechanical properties, and anti-calcification abilities. The grafts retained patency for 1 month of implantation with good endothelialization and anti-calcification properties through upregulating phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling pathway and downregulating tumor necrosis factor (TNF) pathway.