Ph-Responsive Immunomodulatory Hydrogel For Periodontitis

Targeting periodontitis from plaque biofilms causing tissue damage and acidity, and poor conventional drug delivery, this study developed a pH-responsive injectable hydrogel to suppress inflammation via pH-triggered release, providing a minimally invasive strategy. This study designed a pH-responsive hydrogel based on chitosan and oxidized hyaluronic acid, loaded with metformin. The injectability, gel strength, and self-healing properties were characterized by rheological tests. pH-dependent swelling and drug release behavior were validated in vitro under simulated periodontitis acidic conditions (pH 5.0–6.8). Biocompatibility and immunomodulatory functions were evaluated using macrophage cell models, while therapeutic efficacy was confirmed through a rat periodontitis model. The hydrogel remained stable at physiological pH (7.4) but rapidly swelled and released drugs in acidic conditions, enabling targeted delivery. In vitro experiments confirmed excellent biocompatibility and significant suppression of pro-inflammatory factors (TNF-α, IL-6). Western blot revealed its anti-inflammatory mechanism via the AMPK/NF-κB signaling pathway. In vivo, micro-CT showed reduced alveolar bone resorption, while histological analysis confirmed collagen regeneration and decreased inflammatory infiltration. This pH-responsive hydrogel integrates injectability, controlled drug release, and immunomodulatory functions, offering an innovative solution for precise treatment of periodontitis.