title: Controlling Arteriogenesis and Mast Cells Are Central to Bioengineering Solutions for Critical Bone Defect Repair Using Allografts.
abstract: 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 parathyroid 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.
authors.affiliation: US Army Institute of Surgical Research, Multi-Organ Support Technology, 3698 Chambers Pass, Fort Sam Houston, TX 78234, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Antebi
authors.affiliation: Center for Musculoskeletal Research, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Longze
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Sheyn
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Skeletal Biotech Laboratory, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem 91120, Israel.
authors.forename: Gadi
authors.initials: G
authors.lastname: Pelled
authors.affiliation: Center for Musculoskeletal Research, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Xinping
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Skeletal Biotech Laboratory, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem 91120, Israel.
authors.forename: Zulma
authors.initials: Z
authors.lastname: Gazit
authors.affiliation: Center for Musculoskeletal Research, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA; Skeletal Biotech Laboratory, Hebrew University-Hadassah Faculty of Dental Medicine, Jerusalem 91120, Israel.
authors.forename: Dan
authors.initials: D
authors.lastname: Gazit
keywords: arteriogenesis; critical bone defect; fibrosis; mast cells; osteogenesis; recombinant parathyroid hormone (rPTH; teriparatide; Forteo)