Stepwise Assembly of Functional Proteins on Photo-activated TiO2 Surfaces Confers Anti-Oxidative Stress Ability and Stealth Effect to Vascular Stents

Abstract Vascular stents suffer from in-stent restenosis and late thrombosis, which are closely related to adverse foreign body responses and a pathological microenvironment of oxidative stress. To alleviate these problems, we constructed a biological stealth and anti-oxidative stress titanium dioxide (TiO2) vascular stent by the stepwise assembly of functional proteins. In vitro, a photo-activated TiO2 (TiO2-UV) surface with traces of aldehyde groups and superhydrophilicity was used to immobilize the few-layer catalase (approximately 85% surface occupancy) in low secondary structure denaturation and covalent binding (TiO2-UV-CAT). When implanted in vivo, the TiO2-UV-CAT surface unoccupied by catalase selectively immobilized autologous albumin in blood. Autologous albumin was more dominant in competitive adsorption with fibrinogen (FGN) on TiO2-UV-CAT than on TiO2-UNT-CAT (catalase adsorbed untreated TiO2). Based on the synergistic effect of autologous albumin and catalase, TiO2-UV-CAT inhibited fibrinogen-platelet-mediated coagulation, inflammation, oxidative stress, and proliferation of smooth muscle cells (SMCs), and protected endothelial cells (ECs) from free radical damage. In addition, the in vivo inflammatory response to bovine catalase as a heterologous protein on the TiO2-UV-CAT was eliminated. This might have been due to the low secondary structure denaturation of immobilized catalase and the cloaking effect of rat autologous albumin. Finally, TiO2 vascular stents modified with catalase and autologous albumin exhibited excellent biocompatibility in vivo. This stepwise assembly of enzyme and autologous albumin on the photo-activated TiO2 surface could be a feasible surface engineering strategy for vascular stents. The study findings could provide new ideas for tailoring the biological function and improving the biocompatibility of implantable devices.