Neutrophil-Centric Immunomodulatory Nanoplatform Mitigates Implant-Associated Infection and Enhances Osseointegration

The onset of implant-associated infection (IAI) initiates a cascade of immune responses, initially dominated by neutrophils. Bacterial aggregate formation and the presence of a hypoxic microenvironment are two major risk factors in the early stages that can impair neutrophil function, ultimately leading to IAI and implant failure. In this study, we employed a mechanochemical approach to reprogram the implant surface using phytic acid-Zn2+ coordinated nanopillars (PA-Zn@TiNPs) and oxygen self-supporting nanoparticles. The developed PA-Zn@TiNPs combine the anti-bacterial adhesion properties of a superhydrophilic-like surface, the bactericidal effects of the nanopillars, and the chemo-biocidal effects of Zn2+ to inhibit the formation of nascent biofilms. Simultaneously, continuous oxygenation boosted neutrophils with reactive oxygen species, enabling efficient elimination of bacteria both on the implant surface and within neutrophils. This interface effectively reduced infection, accelerated neutrophil apoptosis, and fostered an immunomodulatory osteogenic microenvironment in a rat model of IAI, thereby enhancing bone-implant integration. Therefore, the neutrophil-centric immunomodulation presents a novel template for mitigating implant failure.