3D Biomimetic Calcified Cartilaginous Callus that Induces Type H Vessels Formation and Osteoclastogenesis.

The formation of a calcified cartilaginous callus (CACC) is crucial during bone repair. CACC can stimulate the invasion of type H vessels into the callus to couple angiogenesis and osteogenesis, induce osteoclastogenesis to resorb the calcified matrix, and promote osteoclast secretion of factors to enhance osteogenesis, ultimately achieving the replacement of cartilage with bone. In this study, a porous polycaprolactone/hydroxyapatite-iminodiacetic acid-deferoxamine (PCL/HA-SF-DFO) 3D biomimetic CACC is developed using 3D printing. The porous structure can mimic the pores formed by the matrix metalloproteinase degradation of the cartilaginous matrix, HA-containing PCL can mimic the calcified cartilaginous matrix, and SF anchors DFO onto HA for the slow release of DFO. The in vitro results show that the scaffold significantly enhances angiogenesis, promotes osteoclastogenesis and resorption by osteoclasts, and enhances the osteogenic differentiation of bone marrow stromal stem cells by promoting collagen triple helix repeat-containing 1 expression by osteoclasts. The in vivo results show that the scaffold significantly promotes type H vessels formation and the expression of coupling factors to promote osteogenesis, ultimately enhancing the regeneration of large-segment bone defects in rats and preventing dislodging of the internal fixation screw. In conclusion, the scaffold inspired by biological bone repair processes effectively promotes bone regeneration.