Peptide Polymer-Doped Cement Acting as an Effective Treatment of MRSA-Infected Chronic Osteomyelitis

摘要

Chronic osteomyelitis is a painful and serious disease normally caused by infected surgical prostheses or infected fractures. Currently, antibiotic-loaded cements are extensively used as the treatment in clinical practice. However, the quick emergence of antibiotic-resistant bacteria has resulted in a formidable challenge in treating chronic osteomyelitis, such as the chronic osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA). Aiming to address MRSA-infected chronic osteomyelitis, an antibacterial peptide polymer doped polymethylmethacrylate bone cement pellets (PMMA@polymer) is prepared. The peptide polymer is designed as the synthetic mimic of host defense peptide and enables PMMA@polymer to have notable advantages, including complete release of antibacterial agent from PMMA, potent and robust activity against MRSA even after autoclave and enzymatic treatment, and low susceptibility to antibacterial resistance. PMMA@polymer showed potent in vitro activities against MRSA, superior in vivo therapeutic efficacy in a rabbit chronic osteomyelitis model, and low toxicity during the treatment. These advantages and the easy preparation of PMMA@polymer altogether suggest the great potential of PMMA@polymer as an effective treatment of MRSA-infected chronic osteomyelitis. This study opens new avenues in developing antibacterial biomaterials for the treatment of chronic orthopedic infections, frequently caused by drug-resistant bacteria.