Engineering Neutrophil Function via Oxygen-Generating Implant Surface for Enhanced Osseointegration and Prevention of Implant-Associated Infection

The growing prevalence of implant-associated infection (IAI) in orthopedic surgery presents a serious clinical challenge. This study introduces a novel strategy targeting early risk factors and neutrophil function to enhance bone-implant integration and prevent IAI. Recognizing the crucial role of neutrophils in the early immune response to IAI, we hypothesize that addressing early risk factors like bacterial aggregation and hypoxia can rescue neutrophil function and promote infection resolution. To achieve this, we engineered an implant surface with PA-Zn2+ coordinated TiO2 nanopillar arrays (PA-Zn@TiNPs) and oxygen self-supporting nanoparticles. This modification provides the implant with multiple functionalities: antibacterial adhesion, mechanobactericidal effects, chemobiocidal effects, improved biocompatibility, and enhanced mineralization. Continuous oxygenation facilitated neutrophil bactericidal activity by fueling reactive oxygen species, effectively eradicating bacteria on the implant surface and reducing intracellular infection. Furthermore, local self-oxygenation alleviated hypoxia, accelerating neutrophil apoptosis and promoting M2 macrophage-mediated osteogenesis at the bone-implant interface in vivo. Our strategy pioneers a shift from merely stimulating compromised neutrophils to addressing the root causes of their dysfunction during the early stages of IAI. This tailor-made platform not only prevents IAI but also significantly enhances bone-implant integration, offering a promising solution for orthopedic implants.