Targeting ferroptosis in periodontitis and peri-implantitis: From pathological mechanisms to smart biomaterial interventions for bone regeneration

Abstract

In the pathological microenvironments of periodontitis (PD) and peri-implantitis (PI), achieving precise repair and functional reconstruction of alveolar bone defects remains a major clinical challenge. Ferroptosis, a form of programmed cell death characterized by intracellular free iron overload and lipid peroxidation, has been identified as a key pathogenic factor that disrupts local bone homeostasis and inhibits osteogenic regeneration. However, the exact pathological mechanisms underlying ferroptosis in the pathogenesis and progression of PD/PI remain to be fully elucidated. In recent years, the targeted intervention of ferroptosis using smart biomaterials has emerged as a cutting-edge strategy for achieving tissue-specific repair. This review provides a comprehensive dissection of the pathological cascades and mechanistic crosstalk underlying ferroptosis-driven dysregulation of bone remodeling in PD/PI. Furthermore, it highlights recent advances in the application of advanced ferroptosis-targeting biomaterials, including microenvironment-responsive smart hydrogels, nanoscale delivery systems, and microneedle arrays. The review also critically outlines the existing limitations and challenges of ferroptosis-modulating biomaterials in PI. Crucially, it underscores spatiotemporally controlled strategies engineered into smart biomaterials to synchronize ferroptosis regulation with bone regeneration. Building upon these insights, this review aims to offer forward-looking perspectives for the development of precision clinical therapeutic paradigms endowed with the dual capacity to restore immune homeostasis and promote bone tissue regeneration.