A Microenvironment‐Responsive, Controlled Release Hydrogel Delivering Embelin to Promote Bone Repair of Periodontitis via Anti‐Infection and Osteo‐Immune Modulation

Abstract Periodontitis, a prevalent chronic inflammatory disease, poses significant challenges for effective treatment due to its complex etiology involving specific bacteria and the inflammatory immune microenvironment. Here, this study presents a novel approach for the targeted treatment of periodontitis utilizing the immunomodulatory and antibacterial properties of Embelin, a plant‐derived compound, within an injectable hydrogel system. The developed Carboxymethyl Chitosan‐Oxidized Dextran (CMCS‐OD) hydrogel formed via dynamic chemical bonds exhibited self‐healing capabilities and pH‐responsive behavior, thereby facilitating the controlled release of Embelin and enhancing its efficacy in a dynamic oral periodontitis microenvironment. This study demonstrates that this hydrogel system effectively prevents bacterial invasion and mitigates excessive immune response activation. Moreover, it precisely modulates macrophage M1/M2 phenotypes and suppresses inflammatory cytokine expression, thereby fostering a conducive environment for bone regeneration and addressing periodontitis‐induced bone loss. These findings highlight the potential of the approach as a promising strategy for the clinical management of periodontitis‐induced bone destruction.