▎ 摘 要
Preventing implant-associated infection, which can lead to implant failure and increased medical costs, is one of the biggest challenges in the orthopaedic surgeons. Therefore, the development of stable and highly effective surface modifications to increase the antimicrobial properties of implants is required. In this study, graphene oxide (GO-)-immobilized titanium dioxide (TiO2) was developed to efficiently carry and release antimicrobial drugs. Firstly, tyramine-conjugated GO (GOTA) was synthesized and immobilized onto the surfaces of TiO2 through tyrosinase (Tyr)-catalyzed oxidative reaction (GOTA/TiO2). Doxycycline hyclate (Dox) was then loaded onto GOTA/TiO2 via non-covalent interactions between GO and Dox (Dox/GOTA/TiO2), including electrostatic interaction, pi-pi stacking, hydrophobic interaction, and hydrogen bonds. The amount of loaded drug was able to be controlled, reaching a maximum of 36 mu g/cm(2). in vitro experiments revealed that the sustained release of Dox from the TiO2 surfaces continued for over 30 days. Compared with bare TiO2 and GOTA/TiO2, Dox/GOTA/TiO2 exhibited superior antibacterial activity against both gram-negative Escherichia coli and gram-positive Staphylococcus aureus bacteria, without affecting the viability of human dermal fibroblasts. The obtained results indicated that GO-immobilized TiO2 is an effective carrier for antimicrobial drug delivery to reduce implant associated infection through the synergistic antimicrobial effect of GO and the prescribed drugs.