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

Abstract Severe bone defects remain a significant clinical challenge, necessitating the development of advanced bone repair scaffolds with excellent biocompatibility, precise immune modulation, and robust support for vascularization and osteogenesis. Silk fibroin (SF), a polymer renowned for its outstanding biocompatibility, has been widely used in bone repair scaffold materials. However, its complex fabrication process limits its broader clinical application. In this study, flat silkworm cocoon (FSC), characterized by continuous silk fibers, a porous hierarchical structure, and superior mechanical properties, was utilized for the first time to fabricate bio-scaffolds (TH-PDA@Mg) designed for sustained magnesium ion release in bone repair applications. FSC scaffolds featuring surface pores and extracellular matrix-like structures were successfully prepared using hot-press and surface modification techniques. Magnesium ions were effectively assembled onto FSC scaffolds via polydopamine (PDA)-mediated adhesive interactions. The resulting TH-PDA@Mg scaffolds demonstrated enhanced osteogenic properties, exceptional mechanical strength, superior surface characteristics, and excellent biocompatibility. In vitro analyses revealed that these scaffolds supported cell adhesion, promoted stem cell proliferation, and facilitated osteogenic differentiation due to the synergistic effects of SF and magnesium ions. Furthermore, they exhibited immunomodulatory properties by promoting M2 macrophage polarization while suppressing M1 macrophage activity. In vivo studies using a rat model of critical-sized cranial bone defects showed that the TH-PDA@Mg scaffolds accelerated bone regeneration, enhanced angiogenesis, and mitigated inflammation. These findings highlight the remarkable osteogenic and immunomodulatory potential of functional bio-spinning silk fiber scaffolds, underscoring their promise as a therapeutic strategy for the clinical treatment of bone defects.