Vascularization in the Bone Repair

The repair of critical-size bone defects resulted from severe traumatic injury, infection, surgery for bone cancer or congenital malformation remains a continuous challenge for orthopedists. Currently, autogenous bone grafting is a clinical gold standard for bone repair, and provides excellent osteoconduction, osteoinduction, high-healing rate and absence of immunogenic reaction after surgery. However, autogenous bone grafts are associated with the morbidity of donors, additional surgical procedures for harvest, and limitations in the quantity and available bone size. Bone tissue engineering has become a new and promising alternative approach for the repair of bone defects. Moreover, the clinical application of these advanced technologies in the field of tissue engineering seldom leads to satisfactory results. Increasing evidences have demonstrated that the key factor for the poor repair with tissue-engineered bone is poor vascularization (Nakasa et al. 2005; Kawamura et al. 2006). Bone is a highly vascularized tissue that relies on the supply of essential nutrients and oxygen from blood vessels for maintaining skeletal integrity (Kanczler and Oreffo 2008). Under the circumstance of a well-developed vascular network, the osteoblasts can produce osteoid tissues, differentiate to osteocytes, and form healthy bone. In order to provide sufficient oxygen for survival, osteoblasts must reside within 150-200 mm of a capillary lumen and no cells are greater than 0.2 mm from a blood vessel (Kannan et al. 2005). Without the perfusion of blood supply, the osteoblasts in the middle of tissue-engineered constructs will be necrosis due to ineffective transportation of oxygen, nutrients and metabolites (Smith et al. 2004; Rouwkema et al. 2008). Insufficient vascularization can often restrain the formation of new bones and delay the healing of bones. Therefore, vascularization plays a key role in bone regeneration. The rate and range of vascular growth are the determinants of the efficiency and consequence of new bone formation.