Bio-instructive anti-thrombogenic functionality leveraged by nanocoating of native molecular multiplatform on...

The implantation of neurovascular flow diverters (FDs) has become a new paradigm for endovascular treatment of intracranial aneurysms. However, the implanted FDs still face the biggest challenges regarding thrombosis. Surface modification has been proposed to combat this issue, but the existing research still lacks efficient strategies. Here, a bio-instructive anti-thrombogenic functionality was garnered by a multiplatform nanocoating on FDs, synthesized via the non-covalent co-deposition of specific bioactive molecules-including endothelial-affinity peptides (REDV), vascular endothelial growth factor (VEGF), anti-inflammatory peptides (Chemerin 15), and phosphorylcholine (PC)-onto a copper-incorporated metal-polyphenol network (MPN). Such a multiplatform is supposed to be capable of instructing the formation of a spontaneous surface against acute thrombosis and, more importantly, coordinated endothelialization and anti-hyperplasia through inflammatory regulation, finally achieving long-term healthy homeostasis for vascular remodeling. The in vitro and ex vivo experiments revealed that the coated FDs inhibited adhesion of platelets and fibrinogen as well as their activation, prolonged coagulation time, and prevented thrombus formation. Cell culture demonstrated the coating accelerated FD endothelialization, inhibited smooth muscle cell proliferation, suppressed pro-inflammatory cytokine release and boosted anti-inflammatory cytokine secretion. The overall outstanding anti-thrombogenicity of the coating can be attributed to the nature of the constituent native molecules, the surface/interface characteristics of the nanocoating, and their joint efforts, which together orchestrate the high anti-thrombogenicity of the FD surface over the long run. Our strategy could not only open a new avenue for creating anti-thrombogenic FDs but also underscore the bio-instructive scheme of establishing advanced biomaterial surfaces by making use of functional biophysicochemical cues.