A Polyamine-Capturing Cyclodextrin Hydrogel for Periodontitis Treatment

Periodontitis is a chronic inflammatory disease characterized by a dysregulated interaction between the subgingival microbiota and the host immune response, leading to the accumulation of excessive inflammatory mediators and progressive tissue destruction. In this study, we first established a correlation between polyamine accumulation and periodontal inflammation by testing clinical samples of gingival crevicular fluid. To test the hypothesis that polyamine scavenging will benefit periodontitis treatment, we developed a polyamine-capturing hydrogel loaded with charge modified dodecyl sulfobutyl ether-β-cyclodextrin (SCDC₁₂). The self-assembled SCDC₁₂ nanoparticles effectively alleviated the cellular oxidative stress, improved cell viability, and inhibited the expression of proinflammatory factors by capturing polyamines in vitro. In addition, SCDC₁₂ inhibited the growth of periodontal pathogens and biofilm formation. In a rat periodontitis model, SCDC₁₂ hydrogel inhibited the expression of the rate-limiting enzyme in polyamine anabolism, downregulated the level of proinflammatory factors, and reduced local inflammatory response and alveolar bone loss. Our findings highlight SCDC₁₂ as a promising polyamine scavenger, offering a novel therapeutic strategy for periodontitis treatment by restoring polyamine homeostasis.