Mesoporous TiO 2 Coatings Regulate ZnO Nanoparticle Loading and Zn 2+ Release on Titanium Dental Implants for Sustained Osteogenic and Antibacterial Activity.

Two major issues are currently hindering the clinical practice of titanium dental implants for the lack of biological activities: immediate/early loading risks and peri-implantitis. To solve these issues, it is urgent to develop multifunctional implants modified with effective osteogenic and antibacterial properties. Zinc oxide nanoparticles (ZnO NPs) possess superior antibacterial activity; however, they can rapidly release Zn 2+ , causing cytotoxicity. In this study, a potential dental implant modification was creatively developed as ZnO nanoparticle-loaded mesoporous TiO 2 coatings (nZnO/MTC-Ti) via the evaporation-induced self-assembly method (EISA) and one-step spin coating. The mesoporous TiO 2 coatings (MTCs) regulated the synthesis and loading of ZnO NPs inside the nanosized pores. The synergistic effects of MTC and ZnO NPs on nZnO/MTC-Ti not only controlled the long-term steady-state release of Zn 2+ but also optimized the charge distribution on the surface. Therefore, the cytotoxicity of ZnO NPs was resolved without triggering excessive reactive oxygen species (ROS). The increased extracellular Zn 2+ further promoted a favorable intracellular zinc ion microenvironment through the modulation of zinc transporters (ZIP1 and ZnT1). Owing to that, the adhesion, proliferation, and osteogenic activity of bone mesenchymal stem cells (BMSCs) were improved. Additionally, nZnO/MTC-Ti inhibited the proliferation of oral pathogens (Pg and Aa) by inducing bacterial ROS production. For in vivo experiments, different implants were implanted into the alveolar fossa of Sprague-Dawley rats immediately after tooth extraction. The nZnO/MTC-Ti implants were found to possess a higher capability for enhancing bone regeneration, antibiosis, and osseointegration in vivo . These findings suggested the outstanding performance of nZnO/MTC-Ti implants in accelerating osseointegration and inhibiting bacterial infection, indicating a huge potential for solving immediate/early loading risks and peri-implantitis of dental implants.