Promotion of rat femoral distal bone defect repair using alginate-silk fibroin composite hydrogel

Bone defects, especially those complicated by the inflammatory and immune responses following biomaterial implantation, remain a major challenge in bone regeneration. In this study, we developed Alginate-Silk Fibroin-Graphene Oxide Composite (Alg/SF/GO) hydrogels anchored on the Alg-Tyramine framework, employing HRP/H₂O₂-mediated enzyme crosslinking. These hydrogels demonstrated excellent durability and mechanical properties, along with controllable degradation behavior upon the release of silk fibroin and GO. The Alg/SF/GO hydrogels substantially enhanced osteogenic differentiation and mineralization, while also promoting M2 macrophage polarization and migration via the NF-κB and MAPK pathways. The M2 macrophage polarization induced by these hydrogels facilitated the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) through cytokine secretion. Both in vitro and in vivo experiments showed that Alg/SF/GO hydrogels promoted macrophage infiltration into surrounding tissues, reducing inflammation and fibrous capsule thickening. Ultimately, injecting BMSCs with Alg/SF/GO hydrogels successfully repaired distal femoral defects in rats. This bone-healing biomaterial shows promising potential, particularly for treating irregular bone defects.