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 (Cu²⁺) 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. Cu²⁺ 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⁺, Mg²⁺, and Si⁴⁺ contained in Laponite, which promote osteogenesis and periodontal tissue regeneration. <i>In vitro</i> and <i>in vivo</i> studies confirm that this hydrogel exhibits excellent biocompatibility, effectively inhibits <i>Porphyromonas gingivalis</i>, 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.