Vascularization in Craniofacial Bone Tissue Engineering

Craniofacial bones, separate from the appendicular skeleton, bear a significant amount of strain and stress generated from mastication-related muscles. Current research on the regeneration of craniofacial bone focuses on the reestablishment of an elaborate vascular network. In this review, current challenges and efforts particularly in advances of scaffold properties and techniques for vascularization remodeling in craniofacial bone tissue engineering will be discussed. A microenvironment of ischemia and hypoxia in the biomaterial core drives propagation and reorganization of endothelial progenitor cells (EPCs) to assemble into a primitive microvascular framework. Co-culture strategies and delivery of vasculogenic molecules enhance EPCs' differentiation and stimulate the host regenerative response to promote vessel sprouting and strength. To optimize structural and vascular integration, well-designed microstructures of scaffolds are biologically considered. Proper porous structures, matrix stiffness, and surface morphology of scaffolds have a profound influence on cell behaviors and thus affect revascularization. In addition, advanced techniques facilitating angiogenesis and vaculogenesis have also been discussed. Oxygen delivery biomaterials, scaffold-free cell sheet techniques, and arteriovenous loop-induced axial vascularization strategies bring us new understanding and powerful strategies to manage revascularization of large craniofacial bone defects. Although promising histological results have been achieved, the efficient perfusion and functionalization of newly formed vessels are still challenging.