Development of an injectable salicylic acid-choline eutectic hydrogel for enhanced treatment of periodontitis.

Periodontitis, a chronic inflammatory disease triggered by dental plaque, often presents challenges in management, particularly in severe cases where mechanical debridement alone may be insufficient. As a result, adjunctive therapies, particularly localized drug delivery systems with both antimicrobial and anti-inflammatory properties, are essential to enhance the efficacy of periodontitis management. In this study, we developed a multifunctional hydrogel by incorporating a salicylic acid-choline deep eutectic solvent (DES) into a chitosan/β-glycerol phosphate sodium (CS/GP) hydrogel matrix for the treatment of periodontitis. The DES-CS/GP hydrogel demonstrated favorable physicochemical properties, including gelation and injectability, making it highly suitable for application in the oral cavity. The hydrogel effectively inhibited the growth of key periodontal pathogens, and , and significantly downregulated the expression of pro-inflammatory cytokines TNF-α and IL-1β . Cytocompatibility assessments showed over 80% cell viability in human gingival fibroblasts, human gingival epithelial cells, and human oral keratinocytes over 5 days treated with DES-CS/GP, with fluorescence microscopy confirming robust cytoskeletal integrity. Furthermore, the hydrogel enhanced permeability through gingival tissues In a rat model of periodontitis, the hydrogel significantly mitigated bone loss, reduced bacterial loads of , and suppressed TNF-α and IL-1β expression in gingival tissues. These findings underscore the hydrogel's potential as a safe and effective adjunctive therapy for periodontitis, offering a combination of antimicrobial, anti-inflammatory, and tissue-permeating properties with high biosafety and ease of application.