Abstract: BACKGROUND: During bone tissue healing, promoting the vascularization of new bone is a common strategy to accelerate the repair of bone tissue. However, the rapid fibrosis process during bone defect repair is often ignored.
OBJECTIVE: To design and prepare a core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus, characterize physical characteristics of the scaffold, and verify the anti-fibrosis and osteogenic properties in vitro and in vivo.
METHODS: A core-shell structure bionic scaffold to regulate the process of fibrosis and vascularization in new callus was designed and prepared. The outer shell structure of the scaffold was composed of polycaprolactone electrospun nanofibers loaded with fibroblast activating protein inhibitor; and the inner core structure was composed of gelatin methacrylate hydrogel loaded with deferoxamine. The physical characteristics of electrospun and hydrogel were characterized, and the biocompatibility of the material was verified by live-dead staining and CCK-8 assay. The antifibrotic effect of core-shell structure was analyzed by fibroblast in vitro assay. The osteogenic effect of fibroblast activating protein inhibitor in core-shell structure was analyzed by MC3T3-E1 cells in vitro assay. The vasogenic effect of deferoxamine in core-shell structure was analyzed by human umbilical vein endothelial cells. The effect of bionic core-shell scaffold on bone repair was evaluated by critical bone defect test in rats. 
RESULTS AND CONCLUSION: (1) The core-shell structure bionic scaffold had good biocompatibility. Hydrophobic polycaprolactone electrospun fibers prepared by electrospinning technology could effectively block the ingrowth of exogenous fibrous tissue on the physical level. The electrospun fiber membrane could effectively release the anti-fibrosis drug fibroblast activating protein inhibitor within 2 weeks, and the released anti-fibrosis drug could inhibit the growth and adhesion of fibroblasts around bone defects, effectively reduced the expression of fibroblast-related proteins, promoted the expression of osteoblast protein in MC3T3-E1 cells, and accelerated its mineralization rate. The deferoxamine in the core-shell structure could promote the migration and vascular formation ability of human umbilical vein endothelial cells, and promoted their strong expression of “H” vascular characteristic protein. (2) In critical bone defect model of SD rats established in the femur, compared with polycaprolactone membrane, the core-shell structure bionic scaffold could effectively repair bone defects. (3) These findings indicate that the core-shell structure bionic scaffold can prevent excessive fibrosis of callus and promote the formation of “H” vessels in the new callus, which can effectively avoid the occurrence of nonunion and accelerate the repair process of critical bone defect.

Key words: critical bone defect, core-shell structure bionic scaffold, electrospinning, polycaprolactone, hydrogel, anti-fibrosis, “H”-type , blood vessels