title: Reconstruction of beagle hemi-mandibular defects with allogenic mandibular scaffolds and autologous mesenchymal stem cells.
abstract: OBJECTIVE
  Massive bone allografts are frequently used in orthopedic reconstructive surgery, but carry a high failure rate of approximately 25%. We tested whether treatment of graft with mesenchymal stem cells (MSCs) can increase the integration of massive allografts (hemi-mandible) in a large animal model.
  
  
  METHODS
  Thirty beagle dogs received surgical left-sided hemi-mandibular defects, and then divided into two equal groups. Bony defects of the control group were reconstructed using allografts only. Those of the experimental group were reconstructed using allogenic mandibular scaffold-loaded autologous MSCs. Beagles from each group were killed at 4 (n = 4), 12 (n = 4), 24 (n = 4) or 48 weeks (n = 3) postoperatively. CT and micro-CT scans, histological analyses and the bone mineral density (BMD) of transplants were used to evaluate defect reconstruction outcomes.
  
  
  RESULTS
  Gross and CT examinations showed that the autologous bone grafts had healed in both groups. At 48 weeks, the allogenic mandibular scaffolds of the experimental group had been completely replaced by new bone, which has a smaller surface area to that of the original allogenic scaffold, whereas the scaffold in control dogs remained the same size as the original allogenic scaffold throughout. At 12 weeks, the BMD of the experimental group was significantly higher than the control group (p<0.05), and all micro-architectural parameters were significantly different between groups (p<0.05). Histological analyses showed almost all transplanted allogeneic bone was replaced by new bone, principally fibrous ossification, in the experimental group, which differed from the control group where little new bone formed.
  
  
  CONCLUSIONS
  Our study demonstrated the feasibility of MSC-loaded allogenic mandibular scaffolds for the reconstruction of hemi-mandibular defects. Further studies are needed to test whether these results can be surpassed by the use of allogenic mandibular scaffolds loaded with a combination of MSCs and osteoinductive growth factors.
authors.affiliation: Department of stomatology, General Hospital of the PLA, Beijing, China; Department of Stomatology, The 451th hospital of the People's Libration Army, Xi'an, China.
authors.forename: ChangKui
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of stomatology, General Hospital of the PLA, Beijing, China.
authors.forename: XinYing
authors.initials: X
authors.lastname: Tan
authors.affiliation: Department of stomatology, General Hospital of the PLA, Beijing, China.
authors.forename: JinChao
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of stomatology, General Hospital of the PLA, Beijing, China.
authors.forename: HuaWei
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of stomatology, General Hospital of the PLA, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.affiliation: Department of Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yue
mesh_terms: D000818:Animals; D016025:Bone Transplantation / Q000379:methods*; D004285:Dogs; D008334:Mandible / Q000473:pathology / Q000601:surgery*; D063175:Mandibular Reconstruction / Q000379:methods*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D023421:Models, Animal; D054457:Tissue Scaffolds; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous