title: SDF-1 enhances wound healing of critical-sized calvarial defects beyond self-repair capacity.
abstract: Host blood circulating stem cells are an important cell source that participates in the repair of damaged tissues. The clinical challenge is how to improve the recruitment of circulating stem cells into the local wound area and enhance tissue regeneration. Stromal-derived factor-1 (SDF-1) has been shown to be a potent chemoattractant of blood circulating stem cells into the local wound microenvironment. In order to investigate effects of SDF-1 on bone development and the repair of a large bone defect beyond host self-repair capacity, the BMP-induced subcutaneous ectopic bone formation and calvarial critical-sized defect murine models were used in this preclinical study. A dose escalation of SDF-1 were loaded into collagen scaffolds containing BMP, VEGF, or PDGF, and implanted into subcutaneous sites at mouse dorsa or calvarial critical-sized bone defects for 2 and 4 weeks. The harvested biopsies were examined by microCT and histology. The results demonstrated that while SDF-1 had no effect in the ectopic bone model in promoting de novo osteogenesis, however, in the orthotopic bone model of the critical-sized defects, SDF-1 enhanced calvarial critical-sized bone defect healing similar to VEGF, and PDGF. These results suggest that SDF-1 plays a role in the repair of large critical-sized defect where more cells are needed while not impacting de novo bone formation, which may be associated with the functions of SDF-1 on circulating stem cell recruitment and angiogenesis.
authors.affiliation: Department of Cariology, Restorative Sciences and Endodontics, School of Dentistry, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: Qiming
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, Michigan, United States of America; Department of Biomedical Engineering, College of Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
authors.forename: William V
authors.initials: WV
authors.lastname: Giannobile
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology; D054377:Chemokine CXCL12 / Q000737:chemistry / Q000494:pharmacology*; D003094:Collagen / Q000737:chemistry; D006801:Humans; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000737:chemistry / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000494:pharmacology; D012886:Skull / Q000000981:diagnostic imaging / Q000473:pathology; D014057:Tomography, X-Ray Computed; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects*
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D003094:Collagen