High-strength double-network silk fibroin based hydrogel loaded with Icariin and BMSCs to inhibit osteoclasts and promote osteogenic differentiation to enhance bone repair

Large bone defects cause significant clinical challenges due to the lack of optimal grafts for effective regeneration. The tissue engineering way that requires the combination of biomaterials scaffold, stem cells and proper bioactive factors is a prospective method for large bone repair. Here, we synthesized a three-arm host-guest supramolecule (HGSM) to covalently crosslinking with the naturally derived polymer methacrylated silk fibroin (SFMA). The combination of HGSM and SFMA can form a high strength double-crosslinked hydrogel HGSFMA, that serve as the hydrogel scaffold for bone marrow mesenchymal stem cells (BMSCs) growing. Icariin (ICA) loaded in the HGSFMA hydrogel can promote the osteogenesis efficiency of BMSCs and inhibit the osteoclasts differentiation. Our findings demonstrated that the HGSFMA/ICA hydrogel effectively promoted the in vitro adhesion, proliferation, and osteogenic differentiation of BMSCs. Rat femoral defects model show that this hydrogel can completely repair femoral damage within 4 weeks and significantly promote the secretion of osteogenesis-related proteins. In summary, we have prepared an effective biomimetic bone carrier, offering a novel strategy for bone regeneration and the treatment of large-scale bone defects.