Oxygen-Fueled Neutrophil Empowerment via Mechanochemically Reprogrammed Implant Surface Combats Infection and Enhances Osseointegration

The onset of implant-associated infection (IAI) presents a significant clinical challenge, often leading to impaired osseointegration and implant failure. Neutrophils, key players in the initial immune response, face functional limitations in the hypoxic microenvironment characteristic of the early stages of IAI. This study presents a novel approach to combat IAI by mechanochemically reprogramming the implant surface with phytic acid-Zn2+ coordinated TiO2 nanopillar arrays (PA-Zn@TiNPs) and oxygen self-supporting nanoparticles. This innovative surface modification integrates multiple functionalities to enhance neutrophil performance and prevent infection. The superhydrophilic-like properties of PA-Zn@TiNPs resist bacterial adhesion, while the nanopillars provide bactericidal effects. Additionally, the incorporation of Zn2+ introduces chemo-biocidal properties, further inhibiting the formation of nascent biofilms. Critically, the continuous oxygenation provided by the self-supporting nanoparticles fuels neutrophils with reactive oxygen species (ROS), empowering them to effectively eliminate bacteria both on the implant surface and intracellularly. This multi-pronged approach not only reduces infection but also accelerates neutrophil apoptosis, a crucial step in resolving inflammation and promoting constructive tissue healing. Ultimately, this immunomodulatory strategy creates an osteogenic microenvironment conducive to bone-implant integration in a rat model of IAI. By shifting the paradigm from solely combating bacteria to empowering neutrophils, this study unveils a promising avenue for mitigating implant failure and improving clinical outcomes.