A Novel Strategy to Enhance the Bone Healing Efficacy of Composite Scaffolds via Induction of Cell Recruitment and Vascularization
Abstract
This study devised a novel strategy to develop a functionally improved scaffold that enhances the healing of large bone defects via synergistic activation of vascularization and cell recruitment. To this end, we fabricated round and ring-shaped silk fibroin/Broussonetia kazinoki (SFBK) composite scaffolds. The round scaffolds had a diameter of 1.5 mm, and the ring-shaped scaffolds had a 6-mm diameter with a 1.5-mm hole in the center. All scaffolds had a 3-mm thickness. A portion of round SFBKs was cross-linked with stromal cell-derived factor 1 (SDF-1), and ring-shaped scaffolds underwent in vitro angiogenic stimulation, in vivo vascularization, or both. These scaffolds were assembled by fitting a round SFBK into the center of a vascularized SFBK scaffold before implantation into a rat model with critical-sized calvarial defects. Implantation with puzzle-fitted scaffolds promoted bone regeneration, and the scaffold that underwent both SDF-1 immobilization and vascularization processes showed the greatest efficacy in the healing of defects. The bone healing efficacy of puzzle-fitted scaffolds involved their ability to stimulate microvascular network formation, collagen synthesis, and stem cell recruitment at defects. B. kazinoki-released calcium ions also participated in synergistic bone regeneration. These results suggest that the strategy of fitting SDF-1-linked SFBK into a vascularized ring-SFBK scaffold is useful in recruiting multipotent stem cells via newly formed blood…
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