Antibacterial effect of a copper-containing titanium alloy against implant-associated infection induced by methicillin-resistant Staphylococcus aureus

Implant-associated infection (IAI) induced by methicillin-resistant Staphylococcus aureus (MRSA) is a devastating complication in the orthopedic clinic. Traditional implant materials, such as Ti6Al4V, are vulnerable to microbial infection. In this study, we fabricated a copper (Cu)-containing titanium alloy (Ti6Al4V-Cu) for the prevention and treatment of MRSA-induced IAI. The material characteristics, antibacterial activity, and biocompatibility of Ti6Al4V-Cu were systematically investigated and compared with those of Ti6Al4V. Ti6Al4V-Cu provided stable and continuous Cu2+ release, at a rate of 0.106 mg/cm(2)/d. Its antibacterial performance against MRSA in vitro was confirmed by plate counting analysis, crystal violet staining, and scanning electron microscopic observations. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis demonstrated that Ti6Al4V-Cu suppressed biofilm formation, virulence, and antibioticresistance of MRSA. The in vivo anti-MRSA effect was investigated in a rat IAI model. Implants were contaminated with MRSA solution, implanted into the femur, and left for 6 weeks. Severe IAI developed in the Ti6Al4V group, with increased radiological score (9.6 +/- 1.3) and high histological score (10.1 +/- 1.9). However, no sign of infection was found in the Ti6Al4V-Cu group, as indicated by decreased radiological score (1.3 +/- 0.4) and low histological score (2.3 +/- 0.5). In addition, Ti6Al4V-Cu had favorable biocompatibility both in vitro and in vivo . In summary, Ti6Al4V-Cu is a promising implant material to protect against MRSA-induced IAI. (C) 2020 Published by Elsevier Ltd on behalf of Acta Materialia Inc.