| Summary: | Implant-related infection (IRI) is a major problem in orthopedics. Copper (Cu) is an essential trace element with strong bactericidal activity and, thus, presents potential for reducing IRI. The present study explored a straightforward strategy for releasing Cu<sup>2+</sup> from titanium (Ti) implants, and we conducted a preliminary study to assess the feasibility of this approach in clinical translation. Polylactic acid (PLA) coatings containing different concentrations of copper ions were prepared on Ti discs. The antibacterial activity and biocompatibility of the copper ion-incorporated Ti implants were evaluated using Staphylococcus aureus (<i>S. aureus</i>), bone marrow mesenchymal stem cells (BMSCs) and animal models. In vitro, the coatings produced burst release of Cu<sup>2+</sup> in 12 h, and inhibited <i>S. aureus</i> growth in a dose-dependent manner. The coatings prepared from PLA solutions containing 0.5 or 1.0 mg/mL reduced the viability and osteogenic differentiation of BMSCs, but these effects were negated after the coatings were immersed in culture medium for 6 h. Four weeks after implantation, the Cu-free K-wires challenged with <i>S. aureus</i> had persistent infection and inferior fracture healing to the other three groups, while Cu-coated wires had no evidence of infection. Furthermore, the Cu-coated wires placed in rabbits without <i>S. aureus</i> challenge showed superior fracture healing to the other three groups. These results suggest that PLA coatings containing Cu<sup>2+</sup> may be an effective design for reducing IRI without adversely affecting adjacent bone healing.
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