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

Abstract

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, Porphyromonas gingivalis and Fusobacterium nucleatum, and significantly downregulated the expression of pro-inflammatory cytokines TNF-α and IL-1β in vitro. 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 vitro. In a rat model of periodontitis, the hydrogel significantly mitigated bone loss, reduced bacterial loads of P. g, 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.