Enhancing vascular implants with heparin-polylysine-copper nanozyme coating for synergistic anticoagulation and antirestenotic activity

Re-establishing blood flow through vascular implants, such as stents, faces significant challenges, including late stent thrombosis (LST) and in-stent restenosis (ISR). Strategies to overcome these issues focus on enhancing stent surfaces with anticoagulant, pro-endothelialization, and anti-neointimal hyperplasia (NIH) properties. However, achieving all of these functionalities typically requires complex surface modifications. In this study, we developed nanozyme particles by assembling heparin, polylysine (PLL) and copper ions , which catalytically release nitric oxide (NO) in situ . A functional coating was then formed on pre-deposited polydopamine (PDA) transition layer. Our nanozyme coating not only exhibits robust anticoagulant activity but also enables sustained, in situ release of NO, a critical gas molecule for maintaining vascular health and patency. In vitro results showed that the coating significantly inhibited platelet aggregation, remarkably prolonged activated partial thromboplastin time (APTT), and selectively promoted endothelial cell growth over smooth muscle cells. Ex vivo blood circulation models confirmed its superior anti-thrombotic efficacy, while in vivo experiments further validated its ability to facilitate endothelial regeneration and suppress NIH. This technology offers significant potential for improving the safety and outcomes of cardiovascular implants. • The HPLLCu5 coating, based on heparin-PLL and copper ions , was successfully prepared. • The HPLLCu5 coating provides efficient and sustained in situ NO catalytic release on implants. • The HPLLCu5 coating remarkably prolongs APTT, demonstrating enhanced anticoagulant properties. • The HPLLCu5 coating selectively promotes EC growth over SMCs. • In vivo results confirm its ability to facilitate endothelial regeneration and suppress neointimal hyperplasia.