EGCG-Zn Encapsulated in Plasma-Derived Gel with Enhanced Antibacterial, Anti-Inflammatory, and Osteogenic Effects for the Therapy of Periodontitis

The optimal therapeutic strategy for periodontitis aims to eliminate pathogenic bacteria within periodontal pockets while promoting periodontal tissue regeneration. However, treatment efficacy remains limited due to anatomical constraints within the periodontal environment. Furthermore, antibiotic resistance presents a persistent challenge in clinical management, notwithstanding the status of antibiotics as first-line therapeutics. To thoroughly eliminate bacteria and reduce drug resistance, we prepared a polyphenol-metal coordination hydrogel, namely EGCG-Zn@FG, which consists of a plasma-derived fibrin gel wrapped with epigallocatechin gallate (EGCG) coordinated with zinc ions. The antibacterial efficacy was synergistically enhanced by the intrinsic antimicrobial properties of EGCG combined with the sustained release of zinc ions. Of particular note, EGCG-Zn@FG demonstrated superior antibacterial activity against Porphyromonas gingivalis compared to EGCG-Zn alone. Meanwhile, EGCG-Zn@FG was also shown to have anti-inflammatory effects by reducing the expression of inflammatory factors (IL-1β and IL-6). It is worth mentioning that EGCG-Zn@FG was also verified to upregulate the expression of osteogenic factors (Col-1, ALP, and Runx-2) through the release of EGCG, promoting alveolar bone repair. In rat models, EGCG-Zn@FG in the treatment area was slowly and continuously released for 24 h after administration. Notably, the administration of EGCG-Zn@FG not only exhibited remarkable capability in mitigating dental inflammation and facilitating bone repair, but also ensured favorable biosafety in periodontitis rat models, thereby highlighting its dual advantages in therapeutic efficacy and biocompatibility. Collectively, these findings validate EGCG-Zn@FG as a promising antibiotic-alternative strategy to address antibiotic resistance in periodontitis while possessing substantial potential for clinical treatment of periodontal disease.