Bioinspired channeled, rhBMP-2-coated β-TCP scaffolds with embedded autologous vascular bundles for increased vascularization and osteogenesis of prefabricated tissue-engineered bone

To date, the recovery of large bone defects is a major clinical challenge despite the availability of numerous therapeutic procedures including tissue engineering. Although there is a pressing need for large tissue-engineered constructs, inadequate vascularization remains an insurmountable barrier for successful clinical translation. Considering that vascularization is a prerequisite for osteogenesis, we proposed an advanced design of large customized porous β-tricalcium phosphate (TCP) scaffolds with biomimetic vascular hierarchy which upon embedding of femoral axial vascular bundles significantly improved overall vascularity of the scaffolds. Such scaffolds also promoted osteogenesis when they were coated with recombinant bone morphogenetic protein-2 (rhBMP-2). Compared to the conventional TCP scaffolds (S), the newly designed multi-channeled β-TCP (CS) scaffolds led to adequate blood vessels and bone-like tissue formation throughout their porous hierarchy within 4 weeks of implantation. Especially, the scaffolds coated with rhBMP-2 and embedded with flow-through vascular bundle (FVB) were able to form more uniform vascularized bone within 2 weeks post-implantation. Based on the clinical, radiographic, angiographic and histological assessments, the newly designed multi-channeled scaffolds were found to be promising for successful recovery of large bone defects.