A Redox Amplification Interface Linking Mitochondrial Dysfunction, Immune-Derived Oxidants, and Biomaterial Electrochemistry in Chronic Inflammation

Peri-implant inflammatory disease exhibits marked clinical heterogeneity that cannot be explained solely by microbial burden, indicating the involvement of host-driven amplification mechanisms. This review integrates evidence from redox biology, immunometabolism, and biomaterials science to describe a redox amplification interface (RAI) linking immune-derived reactive oxygen species (ROS), mitochondrial dysfunction, and biomaterial electrochemical reactivity at the host-implant interface. Persistent NADPH oxidase activation promotes mitochondrial oxidative damage, including electron transport chain disruption, cardiolipin oxidation, and ROS-induced ROS release, resulting in sustained intracellular oxidative flux. Mitochondrial dysfunction further contributes to inflammatory amplification through release of damage-associated molecular patterns and activation of inflammasome signaling. Concurrent impairment of antioxidant systems, particularly Nrf2-dependent pathways and glutathione depletion, reduces redox buffering capacity and facilitates propagation of oxidative stress. Inflammatory microenvironments also destabilize implant surface electrochemistry, promoting corrosion, ion release, and surface-mediated redox reactions that increase local oxidative burden. These interacting processes form a coupled system capable of sustaining inflammation independently of the initiating microbial stimulus. This framework provides a mechanistic basis for disease heterogeneity and identifies redox-targeted therapeutic and biomaterial design strategies.