Immune microenvironment modulation for treating inflammatory periodontal bone defects using a dynamic dual-responsive hydrogel

Periodontitis is a chronic inflammatory condition affecting the structures supporting teeth, primarily induced by bacteria. Plaque control and maintenance of local periodontal immune homeostasis are crucial for treating periodontitis and achieving bone regeneration. In this study, we prepared a pH/ROS dual-responsive hydrogel system (CDFBCS@SA) composed of modified carboxymethyl cellulose (CMCDA) and carboxymethyl chitosan (CCS) through dynamic chemical crosslinking to load sinapic acid (SA), a natural phenolic acid with antibacterial and immunomodulatory properties. This hydrogel system can dynamically regulate the long-term and precise release of SA, effectively improve the periodontal inflammatory microenvironment, and enhance its effects in the periodontal microenvironment. <i>In vitro</i> and <i>in vivo</i> experiments demonstrated that this hydrogel system maintains local periodontal immune homeostasis by inhibiting the expression of inflammatory factors, reducing oxidative stress, and regulating macrophage polarization, thereby providing a favorable environment for bone regeneration in the inflammatory periodontal environment and significantly enhancing the regenerative effect of periodontal bone defects. This dynamic cross-linked hydrogel system incorporating SA provides an effective strategy for the regenerative treatment of periodontal bone defects.