Synthetic and Bone tissue engineering graft substitutes: What is the future?

•A history of conventional means for filling critical size bone defects using grafting and bone regeneration techniques.•An introduction as to what materials have so far been used for the creation of bone substitute and vascular augmentation substitutes for a composite bone and vascular void filler.•Possible future directions that will need to be considered in the successful creation of composite vascularized bone void fillers for segmental defects. The management of large segmental bone defects caused by trauma or disease remains clinically challenging within orthopaedics. The major impediment to bone healing with current treatment options is insufficient vascularization and incorporation of graft material. Lack of rapid adequate vascularization leads to cellular necrosis within the inner regions of the implanted material and a failure of bone regeneration. Current treatment options for critical size bone defects include the continued “gold standard” autograft, allograft, synthetic bone graft substitutes, vascularized fibular graft, induced membrane technique, and distraction osteogenesis. Bone tissue engineering (BTE) remains an exciting prospect for the treatment of large segmental bone defects; however, current clinical integration of engineered scaffolds remains low. We believe that the barrier to clinical application of bone tissue engineering constructs lies in the lack of concomitant vascularization of these scaffolds. This mini-review outlines the progress made and the significant limitations remaining in successful clinical incorporation of engineered synthetic bone substitutes for segmental defects.