Treatment of Caries-Induced Pulpal Injury Using a Dynasore-Loaded Bonding System via Regulation of C5a/C5aR Endocytosis

The irreversible inflammation associated with cariogenic pulp injury presents a major challenge in clinical dentistry, as current pulp-capping materials are unable to precisely regulate the early activation of the complement system. To address this limitation, the present study successfully constructed a bisphenol A glycerolate dimethacrylate (Bis-GMA), triethylene glycol dimethacrylate (TEGDMA), 2-hydroxyethyl methacrylate (HEMA), and 10-(methacryloyloxy)decyl dihydrogen phosphate (10-MDP)-based adhesive mixture (BTHM) loaded with the endocytosis inhibitor Dynasore (Dynasore@BTHM). Material characterization (FT-IR, XPS, EDS, DMA, and SEM) confirmed that Dynasore is dispersed within the hydrophobic Bis-GMA/TEGDMA network. Based on these observations, we propose that hydrogen bonding with HEMA enables stable drug loading and may contribute to directional enrichment at the dentin-pulp interface, leading to controlled sustained release. Performance evaluation demonstrated that 2 wt % Dynasore@BTHM exhibits excellent sustained-release characteristics while maintaining favorable mechanical strength, marginal sealing, and biocompatibility. In vitro studies verified that this system inhibits dynamin-mediated endocytosis of C5a/C5aR, effectively down-regulating the expression of EEA-1, C5aR, and the pro-inflammatory cytokine IL-6. Alizarin red staining further indicated its ability to promote pulp cell mineralization. Moreover, in vivo experiments showed that 2 wt % Dynasore@BTHM effectively alleviated inflammatory cell infiltration in pulp tissue and downregulated the expression of key inflammatory factors. Collectively, this study provides a strategy for developing pulp repair materials integrating adhesive function and immunomodulatory capability. By targeting the endocytic pathway, it enables precise and coordinated regulation of the inflammation-regeneration process, thereby exhibiting broad application prospects in the early treatment of cariogenic pulp injury.