Graphene oxide immobilized surfaces facilitate the sustained release of doxycycline for the prevention of implant related infection

Abstract

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, π-π stacking, hydrophobic interaction, and hydrogen bonds. The amount of loaded drug was able to be controlled, reaching a maximum of 36 μg/cm2. 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.