Vascular networks provide nutrients, oxygen, and progenitor cells that are essential for bone function. It has been proposed that a preformed vascular network may enhance the performance of engineered bone. In this study vascular networks were generated from human umbilical vein endothelial cell and mesenchymal stem cell spheroids encapsulated in fibrin scaffolds, and the stability of preformed vascular networks and their effect on bone regeneration were assessed in an in vivo bone model. Under optimized culture conditions, extensive vessel-like networks formed throughout the scaffolds in vitro. After vascular network formation, the vascularized scaffolds were implanted in a critical sized calvarial defect in nude rats. Immunohistochemical staining for CD31 showed that the preformed vascular networks survived and anastomosed with host tissue within 1 week of implantation. The prevascularized scaffolds enhanced overall vascularization after 1 and 4 weeks. Early bone formation around the perimeter of the defect area was visible in X-ray images of samples after 4 weeks. Prevascularized scaffolds may be a promising strategy for engineering vascularized bone.
Keywords: angiogenesis; bone tissue engineering; coculture; mesenchymal stem cells; prevascularization.