<p>TiO<sub>2</sub> Nanotubes Alleviate Diabetes-Induced Osteogenetic Inhibition</p>

Background: Patients with diabetes mellitus (DM) have a higher failure rate of dental implant treatments. However, whether titanium (Ti) implants with TiO 2 nanotubes (TNT) surface can retain their biocompatibility and osteogenetic ability under DM conditions has not been investigated; in addition, their behavior in DM conditions is not well characterized. Materials and Methods: Pure Ti discs were surface treated into the polishing (mechanically polished, MP), sandblasted and acid-etched (SLA), and TNT groups. Scanning electron microscopy was used to examine the surface morphology. The cell adhesion and proliferation ability on different modified Ti surfaces at various glucose concentrations (5.5, 11, 16.5, and 22 mM) was detected by the CCK-8 assay. The osteogenetic ability on different modified Ti surfaces under high-glucose conditions was evaluated by alkaline phosphatase (ALP), osteopontin (OPN) immunofluorescence, Western blot, and Alizarin Red staining in vitro. Detection of cell apoptosis and intracellular reactive oxygen species (ROS) was undertaken both before and after N-acetylcysteine (NAC) treatment to assess the oxidative stress associated with different modified Ti surfaces under high-glucose conditions. An in vivo study was conducted in DM rats with different modified Ti femoral implants. The osteogenetic ability of different modified Ti implants in DM rats was assessed using a micro-CT scan. Results: High-glucose conditions inhibited cell adhesion, proliferation, and osteogenetic ability of different modified Ti surfaces. High-glucose conditions induced higher apoptosis rate and intracellular ROS level on different modified Ti surfaces; these effects were alleviated by NAC. Compared with the SLA surface, the TNT surface alleviated the osteogenetic inhibition induced by high-glucose states by reversing the overproduction of ROS in vitro. In the in vivo experiment, micro-CT scan analysis further confirmed the best osteogenetic ability of TNT surface in rats with DM. Conclusion: TNT surface modification alleviates osteogenetic inhibition induced by DM. It may provide a more favorable Ti implant surface for patients with DM. Keywords: TiO 2 nanotubes, diabetes mellitus, reactive oxygen species, titanium implant, surface modification