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.