Engineering hypoactivated platelet-derived coating to decouple thrombosis for vascular regeneration

The clinical performance of intravascular stents remains limited by thrombotic complications and delayed vascular healing. While cell membrane-based coatings have been explored to recapitulate native biointerfaces, achieving simultaneous hemocompatibility and pro-regenerative functionality remains challenging due to the intrinsic thrombogenicity of platelet-derived materials. Here, we propose a brand-new hypoactivated platelet-derived coating (hPLC) by sequentially assembling fibrin networks and low-activated platelets, followed by controlled lysis to remove pro-thrombotic components. This approach preserves the structural and biointerfacial features of platelet membrane while decoupling thrombogenic activity from regenerative functionality. The resulting hPLC endows materials with reduced protein adsorption, suppressed coagulation, and attenuated inflammatory responses. Transcriptomic analysis further reveals that hPLC enhances endothelial compatibility through coordinated regulation of anti-apoptotic, cytoskeletal remodeling, and angiogenic pathways. In vivo stent implantation studies demonstrate that hPLC-coated stents provide a pro-regenerative microenvironment, significantly accelerating re-endothelialization while inhibiting neointimal hyperplasia and peri-strut inflammation. These findings establish a bioinspired and clinically translatable strategy for engineering multifunctional vascular interfaces from readily available blood components, offering a versatile platform for the surface engineering of vascular devices.