Successful repair of a critical-sized bone defect in the rat femur with a newly developed external fixator

Zhenyu Zhao, Daping Yang, Xu Ma, Hongmei Zhao, Chunlei Nie, Zhenxing Si
Tohoku Journal of Experimental Medicine 2009, 219 (2): 115-20
Regeneration of segmental bone defects has been a clinical challenge. Recent advances in the field of tissue engineering have developed new procedures enabling bone regeneration. Small animal models capable of supporting weight-bearing femoral defects are integral parts of orthopedic biomedical research. However, a drawback of bone healing research is the lack of stable and adaptable fixation devices for small animals. Therefore, we developed and evaluated an adjustable external fixation device in the maintenance of non-healable (ie critical-sized) segmental defects, and in the fixation of tissue-engineered bone grafts in a rat model. Male Sprague-Dawley rats (n = 24) underwent a femoral osteotomy to create a non-healing segmental defect (6 mm size), which was stabilized with the fixator. A treatment group (12 rats) received tissue-engineered bone graft implants consisting of biphasic calcium phosphate blocks seeded with bone mesenchymal stem cells, while other 12 animals received no bone graft (non-treatment group). The osteotomy gap remained unchanged in the non-treatment group over the 12-week period, indicating that the 6-mm bone defect is really non-healable in the rat femur and that the device has sufficient stability for the management of critical-sized femoral defects. At 12 weeks, the treatment group maintained the bone length throughout the study period and showed bridging of the defect, with remarkable new bone formation. In contrast, the non-treatment group showed marginal new bone formation, but no apparent healing. In conclusion, the novel device provides substantial benefits in the maintenance of critical-sized femoral defects and tissue-engineered bone grafts in a rat model.

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