Multifunctional injectable hydrogel incorporating EGCG-Cu complexes for synergistic antibacterial, immunomodulatory, and osteogenic therapy in periodontitis

Periodontitis is a chronic inflammatory disease characterized by oxidative stress, immune system imbalance, and the progressive destruction of periodontal tissues. Traditional treatment approaches are limited by the incomplete eradication of pathogens, the risk of antibiotic resistance, inadequate control of inflammation and oxidative stress, and restricted tissue regeneration capacity. Therefore, this study proposes an injectable multifunctional Laponite/gelatin hydrogel loaded with epigallocatechin gallate (EGCG)-copper ion (Cu 2+ ) complexes as a localized therapy for periodontitis. EGCG exhibits antioxidant, anti-inflammatory, and antimicrobial properties; however, its clinical application is hindered by poor stability and bioavailability. Cu 2+ coordination enhances EGCG stability and antioxidant capacity while improving its antimicrobial efficacy. Experimental results demonstrate that the Laponite/gelatin hydrogel is adaptable for the localized delivery of EGCG-Cu, with bioactive metal ions such as Li + , Mg 2+ , and Si 4+ contained in Laponite, which promote osteogenesis and periodontal tissue regeneration. In vitro and in vivo studies confirm that this hydrogel exhibits excellent biocompatibility, effectively inhibits Porphyromonas gingivalis , suppresses M1 polarization while promoting M2 polarization, and facilitates periodontal tissue repair. Therefore, this study provides promising insights into a localized therapeutic strategy for periodontitis. • Multiple ROS Scavenging Capacity: Cu 2 + catalyzes antioxidant reactions, boosting EGCG’s ability to scavenge reactive oxygen species (ROS), thereby more effectively alleviating oxidative stress. • Injectability and Adaptability: Its adaptability and self-healing properties enable it to fill moist and complex periodontal defects, providing a stable three-dimensional scaffold that promotes cell adhesion and tissue regeneration. • Immunomodulatory Performance: It effectively inhibits M1 polarization of macrophages and promotes their polarization toward the M2 phenotype. • Osteogenic Inductive Function: Cu 2+ and Laponite synergistically exert osteogenic induction, facilitating alveolar bone regeneration in the context of periodontal inflammation. • Biocompatibility: The Lap-Gel/H-E-Cu hydrogel demonstrates good biocompatibility in vitro, showing low toxicity to red blood cells, RAW264.7 cells, and BMSCs. • In Vitro and In Vivo Validation: Through in vitro experiments and animal models, the anti-inflammatory and osteogenic effects of the Lap-Gel/H-E-Cu hydrogel system were validated.