Bone Immune Microenvironment-Modulating Naringin Carbon Dot Complex Hydrogel with ROS-Scavenging and Antibacterial Properties for Enhanced Bone Repair

Bone regeneration involves complex interactions between immune cells and bone lineage cells. Osteoimmunomodulatory strategies that optimize the bone regenerative microenvironment by regulating immune cell behavior represent a key area of research focused on bone repair. In this study, naringin-based copper carbon dots (Nar-CuCDs) were synthesized using the hydrothermal method. Subsequently, Nar-CuCDs were loaded onto a double cross-linked hydrogel (Gel) constructed from acrylamide, sodium alginate oxide, and carboxymethyl chitosan to create a Nar-CuCDs/Gel composite hydrogel. The in vitro experiments indicated that the composite hydrogel had excellent reactive oxygen species (ROS) scavenging properties, anti-inflammatory properties, and osteoimmunomodulatory activity. Nar-CuCDs/Gel could induce anti-inflammatory phenotypic (M2-type) expression in macrophages in an inflammatory environment, regulate the bone immune microenvironment to promote osteogenic differentiation of rBMSCs, thus realizing the synergistic regulation of "immune-osteogenic" for bone repair. In addition, it effectively suppressed the survival of <i>S. aureus</i> and <i>E. coli</i>. Results of in vivo studies showed that the composite hydrogel could accelerate bone regeneration. In conclusion, Nar-CuCDs/Gel potently promoted the repair of bone defects by simultaneously optimizing the immune microenvironment and enhancing osteogenic activity. This strategy of synergistic regulation of "immune-osteogenic" provided insights for bone regeneration research.