Preparation Of TiO₂ Nanotubes Loaded With Copper-zinc And Their Application In Cardiovascular Materials

During the development of cardiovascular interventional devices,many studies began to focus on the functions of anti-inflammation,re-endothelialization,inhibition of intimal hyperplasia and anticoagulation properties on the surface of interventional devices.Loading metal elements as catalysts on the surface of vascular stents can not only avoid the negative effects of high molecular polymer carriers and drug molecules,but also continue to play multiple functions of metal elements.Some studies have shown that copper ions can catalyze the release of nitric oxide from nitric oxide donors,and copper will not be consumed as a catalyst;while zinc ions have exhibited good anti-inflammatory properties.Titanium dioxide nanotubes as an excellent drug carrier,and polydopamine coatings,as a good cross-linking agent,have been widely used in cardiovascular interventional materials surface modification.In order to develop a cardiovascular interventional material with anti-inflammatory,re-endothelialization,inhibition of intimal hyperplasia and anticoagulation properties,we propose a composited of copper-zinc complex-loaded titanium dioxide nanotubes mediated by polydopamine coating,to coordinate play the role of both metal elements.In this paper,highly ordered Ti O₂nanotube arrays were constructed on the surface of titanium substrate by anodization method.Copper was incorporated into Ti O₂nanotubes by solution immersion method.After heat treatment,polydopamine coating loaded with zinc ions was deposited on the surface.The composite coating NTs@Cu-PDA@Zn have been successfully prepared and the surface chemical composition,structure,hydrophilicity and hydrophobicity,ion release and nitric oxide release of the materials were characterized.The biocompatibility of the materials was evaluated by cell culture,blood compatibility experiments and subcutaneous embedding in vivo.The experimental results showed that the composited coating loaded with copper and zinc successfully controlled release of nitric oxide.The composited coating could effectively inhibits platelet adhesion and activation,promoted endothelial cell adhesion and proliferation and inhibited adhesion and proliferation of smooth muscle cells and macrophages.The innovation of this paper is to use Ti O₂nanotubes and polydopamine coating to load copper and zinc ions on Ti O₂nanotubes,and play the role of these two metal elements at the same time.These studies suggest the potential of NTs@Cu-PDA@Zn as a novel composite coating for surface modification of cardiovascular interventional materials.