Mitochondrial-targeted injectable hydrogel for periodontitis therapy via oral immunity and flora regulation

The therapy of chronic periodontitis poses a perennial challenge due to its intricate etiology, specific bacterial involvement, and the presence of an inflammatory immune microenvironment. The misuse of antibiotics not only triggers bacterial resistance but also disrupts the balance of oral microbiota, exacerbating the host's inflammatory response. Herein, a novel integrated synergistic hydrogel delivery platform (named GM/OHA-GZN&M) was designed to facilitate rapid, non-invasive, and antibiotic-free periodontitis treatment. This injectable hydrogel delivery platform fulfils three distinct roles: as a subgingival plaque disruptor, immune microenvironment remodeler, and microbiome modulator. As a subgingival plaque disruptor, GM/OHA-GZN&M hydrogel effectively disrupted bacterial membrane homeostasis, depolarized it, and induced the leakage of materials in the membrane. As an immune microenvironment remodeler, it effectively mediates the targeted clearance of mitochondrial reactive oxygen species (mtROS) through polyphenols, restores mitochondrial function, and disrupts the free radical cycle of inflammation. As a microbiome modulator, it effectively suppressed pathogenic bacterial overgrowth, restored oral gingival microbiota balance in rats, and created a favorable subgingival microenvironment for periodontitis treatment. In <i>in vivo</i> experiments, the GM/OHA-GZN&M hydrogel was used to treat a periodontitis model established by silk thread ligation in rats. Histological, microbiological, and biochemical analyses demonstrated that the hydrogel could significantly suppress inflammation and effectively promote alveolar bone regeneration through immunomodulation. To sum up, this study presents a supports therapeutic potential approach for managing periodontitis.