Thermosensitive 2-Dg-Loaded Hydrogel Attenuates Periodontitis Via Th17 Suppression

Aim or purpose: To investigate the role of IL-17a in immune regulation during periodontitis and develop a novel localized drug delivery system based on glycolysis inhibition for safer and more effective treatment. Materials and methods: IL-17a-deficient mice were constructed to analyze the effects of IL-17a deletion on periodontitis progression. In vitro experiments evaluated the glycolysis inhibitor 2-deoxyglucose (2-DG) for suppressing CD4⁺ T cell proliferation and Th17 differentiation. A thermosensitive PLGA-PEG-PLGA hydrogel encapsulating 2-DG was designed and locally applied to periodontitis models to assess therapeutic efficacy. Results: IL-17a-deficient mice exhibited significantly reduced alveolar bone loss and Th17 cell infiltration. The 2-DG-loaded hydrogel inhibited CD4⁺ T cell proliferation ( p<0.05) and Th17 differentiation ( p<0.05). Local hydrogel application attenuated periodontal inflammation and bone destruction. Conclusions: Exacerbated Th17 differentiation drives periodontitis progression, and targeting glycolysis effectively modulates Th17-mediated immune responses. The 2-DG-encapsulated hydrogel system offers a promising localized strategy for periodontitis treatment, combining immunomodulation with controlled drug release.