A novel antibacterial-immunomodulatory injectable hydrogel for periodontitis management: an in vitro study

BACKGROUND: Considering the limitations of current therapies for periodontitis, this study aimed to design and develop a multifunctional injectable hydrogel based on the pathogenesis of periodontitis. Its biocompatibility, antibacterial, anti-inflammatory and immunomodulatory properties were evaluated in vitro, and its potential for clinical application in periodontitis treatment was further explored. METHODS: The phosphodiesterase-4 (PDE4) inhibitor Apremilast (Apr) and the quaternary ammonium antibacterial agent dimethylaminohexadecyl methacrylate (DMAHDM) were incorporated into methacrylated sodium alginate solutions at varying ratios and thoroughly mixed. A photoinitiator was then added and the mixture was exposed to 405 nm light for 20 s to induce hydrogel formation. The resulting hydrogel extracts were subsequently evaluated for their biocompatibility, antibacterial activity, anti-inflammatory effects and immunomodulatory function. RESULTS: The hydrogel containing 50 µM Apr and 5 µg/mL DMAHDM exhibited excellent biocompatibility and effectively inhibited the growth of the periodontal pathogens Porphyromonas gingivalis and Fusobacterium nucleatum in vitro. qPCR and ELISA revealed that the hydrogel significantly downregulated the mRNA expression of the pro-inflammatory cytokines TNF-α and IL-6, as well as their corresponding protein levels. Moreover, flow cytometry analysis showed that the hydrogel displayed immunomodulatory activity by regulating macrophage polarization, indicating potential anti-inflammatory and immunoregulatory effects. CONCLUSIONS: This novel injectable multifunctional hydrogel demonstrates promising potential for clinical application, offering a new therapeutic strategy for periodontitis treatment.