A Multifunctional Cobalt-Containing Implant for Treating Biofilm Infections and Promoting Osteointegration in Infected Bone Defects Through Macrophage-Mediated Immunomodulation.

Abstract

Treating bone infections and ensuring bone recovery is one of the major global problems facing modern orthopedics. Prolonged antibiotic use may increase the risk of antimicrobial resistance, and inflammation caused by biofilms can obstruct tissue healing, making bone infection treatment even more challenging. The optimal treatment strategy combines immune response modification to promote osteogenesis with effective bacterial infection removal that does not require long-term antibiotic use. A one-step plasma immersion ion implantation approach is used to create titanium alloy implants incorporating cobalt. According to experimental findings, cobalt-containing titanium implants exhibit improved antibacterial activity by efficiently disrupting biofilm formations and reducing Methicillin-resistant Staphylococcus aureus adherence by over 80%. Additionally, the implants exhibit superior anti-inflammatory and osseointegration properties. RNA sequencing analysis reveals the potential mechanism of Co²⁺ in regulating the polarization of macrophages toward the anti-inflammatory M2 phenotype, which is crucial for creating an immune environment conducive to bone healing. Concurrently, these implants promote osteogenic differentiation while suppressing osteoclast activity, further supporting bone repair. Overall, without exogenous recombinant proteins or antibiotics, the implants effectively eradicate infections and expedite bone repair, offering a novel therapeutic strategy for complex skeletal diseases with clinical promise.