ABSTRACT
BACKGROUND: Establishment of a standard experimental animal model of atrophic nonunion is necessary for experimental study and related treatment of atrophic nonunion. However, the common modeling methods cannot accurately simulate atrophic nonunion in the clinical practice. OBJECTIVE: To construct a standard animal model of atrophic nonunion. METHODS: Thirty male Sprague-Dawley rats were randomly divided into experimental and control groups. All animals were subjected to bone cutting at the middle-lower segment of the right tibia and the circular external fixator was applied to keep a 4 mm defect interval. The animals in the experimental group were subjected to an additional cauterization of the periosteum at the fracture end of the tibia with a length of 1 mm. The periosteum was not treated in the control group. The study protocol was approved by the Experimental Animal Ethics Committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine on January 01, 2018, with approval No. TCMF1-2018002. RESULTS AND CONCLUSION: After modeling, there was one case of loose external fixation in each group, and no infection occurred in both groups. Imaging examination showed no bone connection and no sign of healing between the fractures of the tibia in the two groups at 6 weeks after modeling. Imaging and histological findings showed no healing at the end of fracture but typical atrophic nonunion in the experimental group at 12 weeks after modeling. By contrast, six animals had atrophic nonunion, and eight had hypertrophic nonunion in the control group. Overall, the animal model of atrophic tibial nonunion can be successfully constructed using circular external fixator combined with periosteal cauterization at the fracture end.
ABSTRACT
Human adipose tissue-derived mesenchymal stem cell (hATMSC) have emerged as a potentially powerful tool for bone repair, but an appropriate evaluation system has not been established. The purpose of this study was to establish a preclinical assessment system to evaluate the efficacy and safety of cell therapies in a nude rat bone defect model. Segmental defects (5 mm) were created in the femoral diaphyses and transplanted with cell media (control), hydroxyapatite/tricalcium phosphate scaffolds (HA/TCP, Group I), hATMSCs (Group II), or three cell-loading density of hATMSC-loaded HA/TCP (Group III-V). Healing response was evaluated by serial radiography, micro-computed tomography and histology at 16 weeks. To address safety-concerns, we conducted a GLP-compliant toxicity study. Scanning electron microscopy studies showed that hATMSCs filled the pores/surfaces of scaffolds in a cell-loading density-dependent manner. We detected significant increases in bone formation in the hATMSC-loaded HA/TCP groups compared with other groups. The amount of new bone formation increased with increases in loaded cell number. In a toxicity study, no significant hATMSC-related changes were found in body weights, clinical signs, hematological/biochemical values, organ weights, or histopathological findings. In conclusion, hATMSCs loaded on HA/TCP enhance the repair of bone defects and was found to be safe under our preclinical efficacy/safety hybrid assessment system.