Injectable Photocurable Hydrogel For Periodontitis Treatment: Sustained And Potent Antimicrobial

To address the issues of short therapeutic duration and low drug concentration in localized periodontitis treatment, we developed an injectable photocurable hydrogel (Gel/DMA/PL) by integrating ε-poly-L-lysine (PL, broad-spectrum antibacterial agent) and dopamine methacrylamide (DMA, bioadhesive component) into photocurable gelatin methacryloyl (GelMA), aiming to enhance localized antibacterial and anti-inflammatory effects. Synthesized Gel/DMA/PL and characterized its adhesive strength and PL release profile. Evaluated the antibacterial activity of PL against Porphyromonas gingivalis (P. gingivalis) via co-culture, addressing its underexplored role in oral pathogens. Assessed cell viability of human periodontal ligament fibroblasts (hPDLFs) co-cultured with the hydrogel. Established a murine periodontitis model to analyze the hydrogel’s inhibitory effects on alveolar bone resorption and inflammatory infiltration under wet oral conditions. Gel/DMA/PL exhibited rapid photocuring, strong adhesion (60 kPa), and sustained PL release over 20 days. PL demonstrated potent antibacterial activity against P. gingivalis at 0.625 mg/mL. The hydrogel showed excellent cytocompatibility with hPDLFs. In vivo, Gel/DMA/PL significantly reduced bone loss and inflammatory cell infiltration in periodontitis mice. This study is the first to combine PL’s antibacterial properties with the dynamic adhesion of photocurable hydrogels, overcoming the limitations of conventional drugs like poor retention in oral environments. Gel/DMA/PL provides a novel localized strategy with dual "antibacterial–anti-inflammatory" efficacy for periodontitis therapy.