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

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. 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. 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. 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.