Copper-mediated synergistic catalytic titanium dioxide nanofilm with nitric oxide generation and anti-protein fouling for enhanced hemocompatibility and inflammatory modulation

Abstract Nitric oxide (NO) has become a highly compelling therapeutic gas for treating vascular diseases due to its versatile functions to vascular responses. Currently, NO biomimetic materials are successfully established through loading catalyst (i.e., Se, Cu) with the vehicle to decompose endogenous NO donors in blood continuously. However, current NO biomimetic materials are susceptible to the non-specific protein fouling, resulting in undesired therapeutic inefficiency with the observation of attenuated or even blocked NO catalytic activities. Herein, we produced a multifunctional nanofilm with dual catalysis based on the vascular stent platform via simply doping one kind of metal (Cu) as cocatalyst into anatase TiO2 crystal. Beneficial synergistic interactions between two kinds of catalysis are reported in this work. The nanofilm surface is endowed with photoinduced super hydrophilic conversion and controlled NO catalytic release simultaneously. The super hydrophilic surface shows the excellent self-cleaning ability to resist protein fouling. Importantly, the maintenance of the protein-resistant surface can effectively improve the NO catalytic release and reduce inflammatory stimuli, contributing to enhanced hemocompatibility. The optimum doping amount of Cu (TiO2@Cu1, 0.77 wt.%) is determined through the characterization of adjustable photoinduced hydrophilic conversion and appropriate NO catalytic generation within the effective physiological concentration. After vascular implantation in rats, the TiO2@Cu1 nanofilms achieved elevated performances on antithrombosis, reducing the intima hyperplasia area and promoting rapid reendothelialization at 4 weeks. This study provides a valuable guideline for NO-biomimetic materials used for blood contact devices and paves the way for the surface modification for vascular implants.