Bioinspired bilayer 3D printing periosteum scaffold with hierarchical structure based on silk fibroin and sodium alginate for bone regeneration.

The periosteum plays a vital role in fracture repair, particularly in supplying nutrients and facilitating neurovascularization during bone regeneration. Currently, some artificial periosteums exhibit weak mechanical strength, and a lack of neurogenic, angiogenic, and osteogenic functions. In this study, we fabricated a bilayer, bioinspired artificial periosteum composed of a fibrous layer and a cambium layer using 3D printing technique. Methacrylated silk fibroin with high molecular weight, sodium alginate and magenesium ions (SFHGMA/SA/Mg2+) were used to fabricate a double cross-linked network fibrous layer, which exhibits enhanced mechanical strength, low swelling ratio, neurogenesis and angiogenesis. Silk particles, sodium alginate, and mineralized collagen (SFP/SA/MCol) were used to fabricate the cambium layer with a microporous structure improves permeability and osteogenesis. Bilayer bioinspired artificial periosteum was implanted into a critical-size defect in the rat skull, and the results demonstrated this design enhanced angiogenesis, neurogenesis, osteogenesis and bone regeneration at 8 weeks postoperatively. These findings indicate that this bioinspired artificial periosteum could serve as an effective substitute to promote bone repair following periosteal injury.