Biodegradable Zn–Cu alloys show antibacterial activity against MRSA bone infection by inhibiting pathogen adhesion and biofilm formation

Abstract

Bone and joint-related infections remain the primary and most critical complications of orthopedic surgery. We have innovatively prepared Zn-Cu alloys to achieve outstanding material and antibacterial properties. In this study, we systematically assessed the material properties and antibacterial activity of these Zn-Cu alloys. Our results showed that the Zn–2Cu alloy had the best mechanical properties, biocompatibility, and osteogenic properties. Findings of microbial cultures, CLSM, SEM, and TEM indicated that Zn-2Cu alloy can inhibit both coagulase-positive and coagulase-negative staphylococci, as well as antibiotic-resistant strains (MRSA and MRSE), by preventing the bacteria adhesion and the biofilm formation. Zn-2Cu alloy could broadly affect the expression of MRSA genes associated with adhesion, autolysis, biofilm formation, virulence, and drug resistance. A rat femur intramedullary nail infection-prevention model was established and the Zn-2Cu alloy-treated group showed significant antibacterial activity against MRSA and reduced the inflammatory toxic side-effects and infection-related bone loss. Collectively, our results indicate the potential utility of Zn-Cu alloy implants with 2 wt% Cu in treating orthopedic infections.Statement of significance: Osteomyelitis is a serious complication of orthopedic surgeries. Wide use of antibiotics contributes to the appearance of multi-drug resistant strains like methicillin-resistant staphylococcus aureus (MRSA). Alternatively, anti-osteomyelitis implants with broad-spectrum antibacterial properties can be favorable. Here, the antibacterial performance of biodegradable Zn-Cu alloys was evaluated with four different bacteria strains including antibiotic-resistant strains (MRSA and MRSE). Zn-Cu alloys exert excellent bacterial killing capability in all strains. In a rat femur infection model, the alloy showed significant antibacterial activity against MRSA and reduced inflammatory toxic side-effects as well as infection-related bone loss. The antibacterial property of Zn-2Cu alloy was associated with inhibition of gene expression related to wall synthesis, adhesion, colonization, biofilm formation, autolysis, and secretion of virulence factors in MRSA.