Antimicrobial and regenerative copper-doped hybrid biomaterials for bone infection treatment

The bone tissue is endowed with intrinsic regenerative capacity. This is compromised in cases of major alterations like in trauma, surgical removal of cancer lesions, and infections. Osteomyelitis (OM) is an infectious disease of the bone primarily caused by the gram-positive bacterium Staphylococcus aureus and characterized by extensive tissue remodelling and inflammation. Local and systemic antimicrobial treatments are the standard of care; however their efficacy is often limited by immune-mediated vascular damage and biofilm formation. Antimicrobial-loaded biomaterials offer a promising alternative. In this regard, hybrid scaffolds made of hydroxyapatite nanocrystals grown on collagen fibers and mimetic of bone extracellular matrix has already demonstrated to support cell functions and resorb over time. Also, they can be doped with bioactive and antimicrobial ions and release them in a controlled and sustained manner during scaffold degradation and tissue regeneration. In this study, we incorporated Cu²⁺-doped hydroxyapatite into collagen scaffolds (Col/CuHA) with the aim of developing a biomaterial capable at a time to prevent/treat bone infections and promote tissue regeneration. These matrices recapitulated the architecture of bone tissue and released Cu²⁺ ions with bactericidal activity towards a biofilm-forming isolate of Staphylococcus aureus. In vitro experiments in conditions mimicking dynamic fluid exchanges allowed identification of optimal Cu²⁺ loads with balanced antimicrobial activity and cytocompatibility. In vivo preliminary observations from a murine model of ectopic scaffold implantation suggested that these biomaterials can be integrated in the host tissue, thus further corroborating their biocompatibility with the applied loads of Cu²⁺. Our results point to Col/CuHA scaffolds as promising candidates for the prevention and/or treatment of osteomyelitis and the promotion of bone repair, and suggest that they might provide an innovative alternative to conventional antibiotic-based strategies.