Precipitation-Based Silk Fibroin Fast Gelling, Highly Adhesive, and Magnetic Nanocomposite Hydrogel for Repair of Irregular Bone Defects

Critical-sized bone defects, especially for irregular shapes, remain a significant challenge in orthopedics. Although various biomaterials are developed for bone regeneration, their application for repair of irregular bone defects is limited by the complicated preparation procedures involved, and their lack of shape-adaptive capacity, physiological adhesion, and potent osteogenic bioactivity. In the present study, a simple strategy of precipitation by introducing tannic acid (TA) with abundant phenolic hydroxyl groups and Fe 3 O 4 nanoparticles, as metal-phenolic networks (MPN), is developed to easily prepare a fast gelling, shape-adaptive, and highly adhesive regenerated silk fibroin (RSF)/TA/Fe 3 O 4 hydrogel system that can respond to a static magnetic field (SMF). The RSF/TA/Fe 3 O 4 hydrogel exhibits sufficient adhesion in biological microenvironments and good osteogenic effect in vitro and in vivo, under an external SMF, and thus, can be applied to repair critical-sized bone defects. Moreover, bioinformatics analysis reveals that the synergistic mechanism of Fe 3 O 4 NPs and SMF on osteogenic effects can be promotion of osteoblast differentiation via activation of the cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG)/extracellular signal-regulated kinase (ERK) signaling pathway. This study provides a promising biomaterial with potential clinical application for the future treatment of (irregular) critical-sized bone defects.