Redox biology in periodontal inflammation, tissue repair, and bone remodeling: Local-systemic interactions and...

Periodontitis is a biofilm-associated, host-mediated inflammatory disease in which persistent immune activation, extracellular matrix degradation, defective repair, and inflammatory bone loss occur within an accessible tissue environment. Successful healing depends on the timely resolution of inflammation and restoration of tissue architecture; however, disruption of these processes contributes to chronic inflammatory diseases characterized by persistent inflammation, impaired regeneration, and progressive tissue destruction. Among the mechanisms governing these outcomes, redox biology has emerged as an important regulator linking inflammation, cellular function, and tissue remodeling. Reactive oxygen species (ROS) are not solely damaging metabolic byproducts; at controlled levels, they support host defense, cell migration, angiogenesis, and reparative signaling. By contrast, excessive, sustained, or compartmentally dysregulated ROS production promotes oxidative distress, amplifies inflammatory signaling, disrupts epithelial and extracellular matrix integrity, impairs vascular and stromal cell function, enhances osteoclastogenesis, and suppresses osteoblast activity. Periodontal inflammation may also contribute to systemic oxidative and inflammatory burden through circulating mediators, microbial products, and metabolic-immune interactions. This review integrates histological, cellular, metabolic, and bone-remodeling perspectives to propose a periodontitis-centered basis in which the biological effect of ROS depends on their molecular identity, source, concentration, subcellular location, and duration. In addition, current redox-based therapeutic strategies, including antioxidants, antimicrobial photodynamic therapy, and ozone-based approaches are discussed together with their translational limitations and future perspectives. Understanding how redox mechanisms influence tissue architecture and repair may provide new opportunities for the development of targeted therapeutic strategies aimed at restoring tissue homeostasis and improving regenerative outcomes in periodontitis.