Improved Blood Compatibility and Endothelialization of Titanium Oxide Nanotube Arrays on Titanium Surface by Zinc Doping

Titanium dioxide nanotube arrays are widely used in biomaterials due to their unique tubular structure and tunable biocompatibility. In the present study, titanium oxide nanotube arrays with different diameters were prepared on the titanium surface by anodization, followed by zinc doping using hydrothermal treatment to enhance the biocompatibility. Both the nanotube dimensions and zinc doping had obvious influences on the hydrophilicity, protein adsorption, blood compatibility, and endothelial cell behaviors of the titanium surface. The increase of the diameter and zinc doping can improve the hydrophilicity of the titanium surface. The increase of nanotube diameter could reduce the albumin adsorption while increasing the fibrinogen adsorption. However, zinc doping can simultaneously promote the adsorption of albumin and fibrinogen, and the effect was more obvious for albumin. Zinc doping can significantly improve the blood compatibility of the titanium oxide nanotubes because it cannot only increase the activity of cyclophosphate guanylate (cGMP) but also significantly reduce the platelets adhesion and hemolysis rate. Moreover, it was also found that both the smaller diameter and zinc doping nanotubes can enhance the endothelial cell adhesion and proliferation as well as up-regulate the expression of NO and VEGF. Therefore, the zinc doped titanium dioxide nanotube array can be used to simultaneously improve the blood compatibility and promote endothelialization of the titanium-based biomaterials and implants, such as intravascular stents.