An injectable, photopolymerizable, and adhesive hydrogel for sustained antimicrobial ε-poly-l-lysine delivery in periodontitis therapy.

Periodontitis, a chronic inflammatory disease caused by periodontal pathogens, is characterized by alveolar bone resorption and tooth loss. Effective drug delivery to hidden pathogens is significantly hindered by several factors, including increasing antibiotic resistance, the complex and moist oral environment, and the deep, narrow nature of periodontal pockets. Herein, an injectable, adhesive, photopolymerizable and antibacterial hydrogel (Gel/DMA/PL) was synthesized by loading ε-poly-l-lysine (PL) onto dopamine methacrylamide (DMA)-grafted gelatin methacryloyl (GelMA). This hydrogel enabled sustained antibacterial activity through mechanical retention, catechol-mediated bioadhesion, and sufficient local antibacterial concentration, thereby inhibiting periodontal pathogenesis. The adhesive properties of the hydrogel also facilitated effective hemostasis on bleeding wound surfaces within the inflammatory milieu of periodontitis. Bacterial coculture experiments demonstrated potent antibacterial activity against representative periodontal pathogens. Cytotoxicity and hemocompatibility assays exhibited excellent biocompatibility. Histological and quantitative polymerase chain reaction analysis further revealed that the hydrogel significantly suppressed bacterial colonization, subsequently downregulated proinflammatory cytokines, and thus reduced alveolar bone resorption in a murine model of periodontitis. By enabling sustained local antimicrobial delivery within periodontal pockets, the Gel/DMA/PL hydrogel offers an effective localized therapeutic strategy for periodontitis.