Locally Delivered Hydrogel with Sustained Release of Flavonol Compound Kaempferol Mitigates Inflammatory Progression of Periodontitis and Enhances the Gut Microflora Composition in Rats

OBJECTIVE: This study aimed to investigate the effects of a sustained-release composite containing gelatin methacryloyl (Gel) and kaempferol (Ka, K) on experimental periodontitis symptoms in rats. METHODS: Forty 6-week-old male rats were randomly assigned to four treatment groups in a specific pathogen-free (SPF) environment: Control group (C), periodontitis model group (M), Gel alone group (G), and Gel_Ka composite-treated group (G_K). Treatment effects on the periodontal status of bilateral maxillary second molars in each rat group were assessed by micro-CT imaging and histology. Immunohistochemistry staining was employed to examine the effects on expression levels of inflammatory factors IL-6 and MMP9 (associated with M1 macrophages) and of the anti-inflammatory factor CD206 (associated with M2 macrophages). Additionally, treatment effects on oral and intestinal microbial communities were analyzed through 16S rDNA sequencing. RESULTS: Local injection treatment with the G_K composite hydrogel effectively suppressed alveolar bone resorption and reduced periodontal attachment loss and inflammation infiltration in rats with periodontitis. It reduced the expression of inflammatory factors MMP9 and IL-6 but increased the anti-inflammatory factor CD206, and it also increased the abundance of gut microbial communities producing short-chain fatty acids. CONCLUSION: Local treatment with the sustained-release G_K hydrogel composite demonstrates a substantial antiperiodontitis effect in rats by locally attenuating inflammation and is associated with enhancing the microbial composition of intestinal flora, thus aiding in mitigating the inflammatory progression of experimental periodontitis.