Photofunctionalized and Drug-Loaded TiO₂ Nanotubes with Improved Vascular Biocompatibility as a Potential Material for Polymer-Free Drug-Eluting Stents

Implantation of a drug-eluting stent is the most common treatment method for patients with cardiovascular atherosclerosis. However, this treatment may delay re-endothelialization, and the drug polymer-coated stent may induce thrombosis months after a stent implantation. The development of polymer-free drug-eluting stents is a promising approach to overcome these shortcomings. Titanium dioxide nanotubes (TiO₂-NTs) are excellent drug carriers and have been considered as a potential material for polymer-free drug-eluting stents. However, TiO₂-NTs reportedly induce severe blood clotting, which is a significant shortcoming for use as a stent. Vascular stents must be compatible with blood and must have antibacterial, anti-inflammatory, and selective inhibitory activities in the abnormal hyperplasia of smooth muscle cells, instead of delaying the re-endothelialization of endothelial cells. To meet these requirements, we presented a composite material that featured ultraviolet (UV) irradiation of TiO₂-NTs-containing silver nanoparticles (AgNPs). The AgNPs were loaded in the lumen of TiO₂-NTs as a representative compound to suppress the inflammatory response and hyperplasia. UV irradiation was performed as a novel method to improve the anticoagulant ability of the AgNP-loaded TiO₂-NTs. The chemical state and biocompatibility of the UV-TiO₂-NTs@AgNPs were evaluated. UV irradiation strongly improved the anticoagulant ability of the TiO₂-NTs and moderated the release of Ag⁺ from AgNPs, which selectively suppressed the inflammatory response and hyperplasia. Furthermore, the UV-TiO₂-NTs@AgNPs-2 displayed enhanced biocompatibility evidenced by the inhibition of platelet adhesion, bactericidal activity, selective suppression of the smooth muscle cell proliferation, and inhibition of the adhesion of macrophages. The collective findings indicate the potential of the photofunctionalized TiO₂-NTs loaded with AgNPs as a material for polymer-free drug-eluting stents.