title: Establishment of a bilateral femoral large segmental bone defect mouse model potentially applicable to basic research in bone tissue engineering.
abstract: BACKGROUND
  To understand the cellular mechanism underlying bone defect healing in the context of tissue engineering, a reliable, reproducible, and standardized load-bearing large segmental bone defect model in small animals is indispensable. The aim of this study was to establish and evaluate a bilateral femoral defect model in mice.
  
  
  METHODS
  Donor mouse bone marrow mesenchymal stem cells (mBMSCs) were obtained from six mice (FVB/N) and incorporated into partially demineralized bone matrix scaffolds to construct tissue-engineered bones. In total, 36 GFP(+) mice were used for modeling. Titanium fixation plates with locking steel wires were attached to the femurs for stabilization, and 2-mm-long segmental bone defects were created in the bilateral femoral midshafts. The defects in the left and right femurs were transplanted with tissue-engineered bones and control scaffolds, respectively. The healing process was monitored by x-ray radiography, microcomputed tomography, and histology. The capacity of the transplanted mBMSCs to recruit host CD31(+) cells was investigated by immunofluorescence and real-time polymerase chain reaction.
  
  
  RESULTS
  Postoperatively, no complication was observed, except that two mice died of unknown causes. Stable fixation of femurs and implants with full load bearing was achieved in all animals. The process of bone defect repair was significantly accelerated due to the introduction of mBMSCs. Moreover, the transplanted mBMSCs attracted more host CD31(+) endothelial progenitors into the grafts.
  
  
  CONCLUSIONS
  The present study established a feasible, reproducible, and clinically relevant bilateral femoral large segmental bone defect mouse model. This model is potentially suitable for basic research in the field of bone tissue engineering.
authors: National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopedics, Southwest Hospital, the Third Military Medical University, Chongqing, China; Laboratory of Tissue Engineering in Chongqing City, Chongqing, 400038, China; Center of Regenerative and Reconstructive Engineering Technology in Chongqing City, Chongqing, 400038, China.
authors: Junchao
authors: J
authors: Xing
authors: National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopedics, Southwest Hospital, the Third Military Medical University, Chongqing, China; Laboratory of Tissue Engineering in Chongqing City, Chongqing, 400038, China; Center of Regenerative and Reconstructive Engineering Technology in Chongqing City, Chongqing, 400038, China; Department of Orthopaedics, No. 519 Hospital of PLA, Xichang, 615000, China.
authors: Huiyong
authors: H
authors: Jin
authors: National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopedics, Southwest Hospital, the Third Military Medical University, Chongqing, China; Laboratory of Tissue Engineering in Chongqing City, Chongqing, 400038, China; Center of Regenerative and Reconstructive Engineering Technology in Chongqing City, Chongqing, 400038, China. Electronic address: tianyonghou@126.com.
authors: Tianyong
authors: T
authors: Hou
authors: National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopedics, Southwest Hospital, the Third Military Medical University, Chongqing, China; Laboratory of Tissue Engineering in Chongqing City, Chongqing, 400038, China; Center of Regenerative and Reconstructive Engineering Technology in Chongqing City, Chongqing, 400038, China.
authors: Zhengqi
authors: Z
authors: Chang
authors: National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopedics, Southwest Hospital, the Third Military Medical University, Chongqing, China; Laboratory of Tissue Engineering in Chongqing City, Chongqing, 400038, China; Center of Regenerative and Reconstructive Engineering Technology in Chongqing City, Chongqing, 400038, China.
authors: Fei
authors: F
authors: Luo
authors: National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopedics, Southwest Hospital, the Third Military Medical University, Chongqing, China; Laboratory of Tissue Engineering in Chongqing City, Chongqing, 400038, China; Center of Regenerative and Reconstructive Engineering Technology in Chongqing City, Chongqing, 400038, China.
authors: Pinpin
authors: P
authors: Wang
authors: National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopedics, Southwest Hospital, the Third Military Medical University, Chongqing, China; Laboratory of Tissue Engineering in Chongqing City, Chongqing, 400038, China; Center of Regenerative and Reconstructive Engineering Technology in Chongqing City, Chongqing, 400038, China.
authors: Zhiqiang
authors: Z
authors: Li
authors: National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopedics, Southwest Hospital, the Third Military Medical University, Chongqing, China; Laboratory of Tissue Engineering in Chongqing City, Chongqing, 400038, China; Center of Regenerative and Reconstructive Engineering Technology in Chongqing City, Chongqing, 400038, China.
authors: Zhao
authors: Z
authors: Xie
authors: National and Local United Engineering Laboratory of Tissue Engineering, Department of Orthopedics, Southwest Hospital, the Third Military Medical University, Chongqing, China; Laboratory of Tissue Engineering in Chongqing City, Chongqing, 400038, China; Center of Regenerative and Reconstructive Engineering Technology in Chongqing City, Chongqing, 400038, China. Electronic address: jianzhongxu@163.com.
authors: Jianzhong
authors: J
authors: Xu
mesh_terms: D000818:Animals; D001860:Bone Plates; D016025:Bone Transplantation / Q000379:methods; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000601:surgery / Q000628:therapy; D005269:Femur / Q000000981:diagnostic imaging / Q000293:injuries / Q000601:surgery; D017102:Fracture Healing; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D010012:Osteogenesis; D019736:Prostheses and Implants; D011859:Radiography; D015203:Reproducibility of Results; D023822:Tissue Engineering / Q000379:methods*; D016474:Weight-Bearing
chemical_list: D049452:Green Fluorescent Proteins
keywords: Bilateral bone defect; Mesenchymal stem cells; Mouse model; Tissue engineering