Infection-prevention on Ti implants by controlled drug release from folic acid/ZnO quantum dots sealed titania nanotubes

Highlights: • A pH-sensitive ZnO-FA sealed TNTs system was fabricated, the TNTs acted as the loading platform and loaded vancomycin. • The antibacterial ratio of TNTs-Van@ZnO-FA against S. aureus is enhanced from 60.8% to 98.8% as the pH value decreased. • The release of Van could be controlled by the pH value of environments. • This system can provide long-term bacterial infection-prevention. - Abstract: Bacterial infections and related complications are predominantly responsible for the failure of artificial biomaterials assisted tissue regeneration in clinic. In this work, a hybrid surface system is applied to prolong the drug release duration from dug-loaded titania nanotubes and thus to prevent Ti implants-associated bacterial infections. This feature is endowed by conjugating folic acid (FA) onto the surface of ZnO quantum dots (QDs)-NH₂ via an amidation reaction. Titania nanotubes (TNTs) loaded with vancomycin (Van) are capped by these FA functionalized ZnO (ZnO-FA) QDs that keep stable in normal physiological environments but dissolves to Zn^{2 +} in the mildly acidic environment after bacterial infections as validated by the drug release profile. The antibacterial ratio of TNTs-Van@ZnO-FA QDs against Staphylococcus aureus is enhanced from 60.8% to 98.8%while this value is only increased from 85.2% to 95.1% for TNTs-Van once the pH value of the environment is decreased from 7.4 to 5.5. This is due to the synergistic effects of Van and Zn²⁺ because the gradual dissolution of ZnO-FA caps on TNTs with the decrease of pH value can induce the acceleration of both Van and Zn²⁺ release. In addition, this TNTs-Van@ZnO-FA system also exhibits excellent biocompatibility because of the folic acid and sustained release of Zn ions. Hence, this surface system can be potentially used as a promising bioplatform on Ti-based metallic implants to prevent bacterial infection with a long-lasting effect.