Nano-CaO2 Coating for Oxygen Support in Peri-Implant Infections: Regulating Neutrophil Apoptosis and Intracellular Sterilization

Hypoxic conditions may impair ROS synthesis, leading to decreased ROS levels that enable bacteria to evade neutrophil-mediated killing (6, 14). Furthermore, phagocytes can act as a 'Trojan horse' and serve as immune-privileged reservoirs for engulfed germs, potentially resulting in intracellular infection and ongoing transmission (37). In addition to inhibiting biofilm formation, we emphasize that eliminating intracellular bacteria is also crucial for preventing IAI, especially under hypoxic conditions. Unlike targeted drug delivery systems for anti-intracellular bacteria (48), we propose a simple and smart strategy involving the in-situ deposition of nano-CaO2 on the implant surface to provide oxygen support. Our findings demonstrate that nano-CaO2 deposition can alleviate hypoxic conditions, increase neutrophil ROS, and effectively reduce the survival rate of bacteria both on the implant surface and inside neutrophils.

The hypoxic microenvironment delays neutrophil apoptosis (49), which, in turn, can prolong the inflammatory process and impair tissue repair (50, 51). Although there are inhibitors available to attenuate neutrophil survival (52, 53), local oxygenation may represent a more direct and rational approach to reducing neutrophil persistence in inflammatory diseases (50). However, hastening neutrophil apoptosis in infectious inflammation also raises concerns about the spread of infection (54-56). In the pathogenesis of IAI, the impact of peri-implant oxygenation on neutrophil functions prior to neovascularization remains largely unknown. In this study, we demonstrate that an oxygen self-supporting coating on the implant can regulate neutrophil apoptosis and intracellular sterilization under infectious conditions, thereby promoting the resolution of inflammation in the early post-operative phase.