Abstract

Chopped fiber (CF)- and nano-hydroxyapatite (n-HA)-enhanced silk fibroin (SF) porous hybrid scaffolds (SHCF) were prepared by freeze-drying for bone augmentation. Compared with pristine SF scaffolds, the incorporation of CF and n-HA can significantly enhance the mechanical properties of the composite scaffold. The results of cell experiments and mouse subcutaneous implantation indicated that the SHCF could alleviate foreign body reactions (FBR) led by macrophages and neutrophils, promote the polarization of RAW264.7 cells to anti-inflammatory M2 macrophages, and inhibit the secretion of pro-inflammatory cytokine TNF-α. A rat femoral defect repair model and bulk-RNA-seq analysis indicated that the CF- and n-HA-enhanced SHCF promoted the proliferation and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) by the upregulation of Capns1 expression and regulated the calcium signaling pathway to mediate osteogenesis-related cell behavior, subsequently promoting bone regeneration.

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