Mechanochemically Reprogrammed Interface Orchestrates Neutrophil Bactericidal Activity and Apoptosis for Preventing Implant-Associated Infection

The onset of implant-associated infection (IAI) triggers a cascade of immune responses, which are initially dominated by neutrophils. Bacterial aggregate formation and hypoxic microenvironment, which occur shortly after implantation, may be two major risk factors that impair neutrophil function and lead to IAI. Here, the implant surface with phytic acid-Zn2+ coordinated TiO2 nanopillar arrays (PA-Zn@TiNPs) and oxygen self-supporting CaO2 nanoparticles, named as CPZTs, is mechanochemically reprogrammed. The engineered CPZTs interface integrates multiple properties to inhibit the formation of nascent biofilm, encompassing antibacterial adhesion, mechanobactericidal effect, and chemobiocidal effect. Meanwhile, continuous oxygenation fuels the neutrophils with reactive oxygen species (ROS) for efficient bacterial elimination on the implant surface and inside the neutrophils. Furthermore, this surface modulation strategy accelerates neutrophil apoptosis and promotes M2 macrophage-mediated osteogenesis both in vitro and in a rat model of IAI. In conclusion, targeting neutrophils for immunomodulation is a practical and effective strategy to prevent IAI and promote bone-implant integration. The implant surface with phytic acid-Zn2+ coordinated nanopillars and oxygen self-supporting nanoparticles, named as CPZTs, is mechanochemically reprogrammed. CPZTs prevent implant-associated infection by repelling bacterial adhesion, killing attached bacteria, and facilitating neutrophil bactericidal activity. Meanwhile, self-supporting oxygen allows neutrophils to orchestrate intracellular bactericidal activity and apoptosis under hypoxia, contributing to inflammation resolution.image