Apremilast-DMAHDM hydrogel inhibits periodontal pathogens and downregulates pro-inflammatory cytokines in vitro.

Current therapies for periodontitis, a chronic inflammatory disease characterized by alveolar bone resorption and tooth loss, face significant limitations. These include increasing antibiotic resistance and challenges in effective drug delivery to hidden pathogens within the complex oral environment. Standard treatments often fall short in addressing both the bacterial infection and the destructive inflammatory response. This study aimed to develop a multifunctional injectable hydrogel that could simultaneously target bacterial pathogens and modulate the host immune response, offering a novel strategy to overcome these therapeutic gaps.

Researchers designed an injectable hydrogel by incorporating the phosphodiesterase-4 (PDE4) inhibitor Apremilast (Apr) and the quaternary ammonium antibacterial agent dimethylaminohexadecyl methacrylate (DMAHDM) into methacrylated sodium alginate solutions. A photoinitiator was added, and the mixture was exposed to 405 nm light for 20 s to induce hydrogel formation. The resulting hydrogel extracts, specifically those containing 50 µM Apr and 5 µg/mL DMAHDM, were then evaluated in vitro. Assays included biocompatibility testing, antibacterial activity against Porphyromonas gingivalis and Fusobacterium nucleatum, anti-inflammatory effects via qPCR and ELISA for TNF-α and IL-6, and immunomodulatory function using flow cytometry to assess macrophage polarization.

The developed hydrogel, specifically the formulation containing 50 µM Apr and 5 µg/mL DMAHDM, exhibited excellent biocompatibility, indicating its safety for cellular interactions. This hydrogel effectively inhibited the growth of key periodontal pathogens, Porphyromonas gingivalis and Fusobacterium nucleatum, demonstrating potent antibacterial activity in vitro. Further analysis using 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. This suggests a strong anti-inflammatory effect. Moreover, flow cytometry analysis provided compelling evidence of the hydrogel's immunomodulatory capabilities. > The hydrogel displayed immunomodulatory activity by regulating macrophage polarization, shifting immune cells towards a more reparative or anti-inflammatory phenotype. These combined effects highlight the hydrogel's potential to not only combat infection but also mitigate the destructive inflammatory processes central to periodontitis pathogenesis.