Functionalized bio-spinning silk fiber scaffolds containing Mg2+with osteoimmunomodulatory and osteogenesis abilities for critical-sized bone defect regeneration

Abstract The repair of severe bone defects poses a significant clinical challenge. Excellent bone repair scaffold materials demand exceptional biocompatibility, precise immune response regulation, and the capability to promote blood vessel and bone regeneration. Silk fibroin, a polymer exhibiting excellent biocompatibility, is widely utilized in bone repair scaffold materials. However, its complex preparation process limits its extensive clinical application. In this study, flat silkworm cocoon (FSC) with continuous silk fibers, a porous hierarchical structure, and superior mechanical properties was employed for the first time to develop bio-scaffolds (TH - PDA@Mg) capable of sustained magnesium ion release for bone repair applications. We demonstrated that FSC scaffolds could be size-adjusted and possessed a structure analogous to the extracellular matrix through hot press and surface modification techniques. Additionally, magnesium ions were successfully self-assembled onto the FSC scaffolds via polydopamine (PDA) - mediated adhesive attraction. The constructed TH - PDA@Mg scaffolds exhibited enhanced osteogenesis capabilities along with high mechanical strength, excellent surface properties, and superior biocompatibility. In vitro experiments indicated that the TH - PDA@Mg scaffolds supported cell attachment while promoting the proliferation and osteogenic differentiation of stem cells due to the combined effects of silk fibroin and magnesium ions. Moreover, they exerted immunomodulatory effects by promoting M2 macrophage polarization while suppressing M1 macrophage polarization. In vivo studies using a rat model with critical - size cranial bone defects revealed that the TH - PDA@Mg scaffolds accelerated bone regeneration, enhanced angiogenesis, and reduced inflammation. These findings underscore the potent osteogenic - promoting abilities and immunomodulatory properties of functional bio - spinning silk fiber scaffolds, suggesting their potential as a therapeutic strategy for future clinical treatment of bone defects.