Bone tissue engineering application with the vasculogenesis inducing biphasic scaffold

Bone has a self-healing capacity regenerating itself without leaving a scar. However, critical size defects due to trauma, tumor, disease or infection require bone graft surgeries in which complication rate is high. Bone tissue engineering is thought to be as an alternative for grafting. On the other hand, upon implantation, bone tissue engineering constructs or the grafts generally fail due to insufficient vascularization. Vasculogenesis is important in bone fracture healing which supplies the requirements of the oxygen and nutrient, direct inflammatory signals and cells to the wound site. Vasculogenesis occurs through migration of endothelial cells to the defect site by sensing the signals for inadequate vascularization. One of the strategies to provide vasculogenesis in tissue engineering constructs is to employ environments or angiogenic factors to induce cells to migrate to the defect site. In this strategy a bone tissue engineering scaffold should be designed appropriately by allowing the endothelial cell migration to form vessels. In addition, correct choice of angiogenic factors and their correct combination is also an important step for this strategy. Vascular endothelial growth factor (VEGF) can be used to induce vasculogenesis in tissue engineering constructs. Due to the short half life of those growth factors, sustained release systems or gene therapy methods can be used for the delivery of angiogenic factors. In this study, a fibrous bone tissue engineering scaffold was produced using poly(lactic acid-co-glycolic acid) (PLGA) and rat bone marrow-derived mesenchymal stem cells (rBMSCs) were seeded on it. PLGA and poly(ethylene glycol) (PEG) based hydrogel polymerized around PLGA scaffold, and was used for the sustained release of VEGF activator GS4012. Designed scaffold and sustained release system were tested in vitro conditions with endothelial cells isolated from rat peripheral blood (rPBECs) for their migration and microvessel formation ability. After that, the designed system was used to engineer a vascularized bone on critical sized defects on rat crania. This study showed that the usage of VEGF inducer GS4012 facilitated the migration of endothelial cells and led to the occurrance of vasculogenesis that also help the formation of new bone tissue.