Controlling Arteriogenesis and Mast Cells Are Central to Bioengineering Solutions for Critical Bone Defect Repair Using Allografts

Ben Antebi, Longze Zhang, Dmitriy Sheyn, Gadi Pelled, Xinping Zhang, Zulma Gazit, Edward Schwarz, Dan Gazit
2016 Bioengineering  
Although most fractures heal, critical defects in bone fail due to aberrant differentiation of mesenchymal stem cells towards fibrosis rather than osteogenesis. While conventional bioengineering solutions to this problem have focused on enhancing angiogenesis, which is required for bone formation, recent studies have shown that fibrotic non-unions are associated with arteriogenesis in the center of the defect and accumulation of mast cells around large blood vessels. Recently, recombinant
more » ... yroid hormone (rPTH; teriparatide; Forteo) therapy have shown to have anti-fibrotic effects on non-unions and critical bone defects due to inhibition of arteriogenesis and mast cell numbers within the healing bone. As this new direction holds great promise towards a solution for significant clinical hurdles in craniofacial reconstruction and limb salvage procedures, this work reviews the current state of the field, and provides insights as to how teriparatide therapy could be used as an adjuvant for healing critical defects in bone. Finally, as teriparatide therapy is contraindicated in the setting of cancer, which constitutes a large subset of these patients, we describe early findings of adjuvant therapies that may present future promise by directly inhibiting arteriogenesis and mast cell accumulation at the defect site.
doi:10.3390/bioengineering3010006 pmid:28952568 fatcat:orxmszsljzedfikmcrkmofsiom