Development of a reliable non-union model in mice

Background. Despite the growing knowledge of the mechanisms of fracture healing, non-unions remain a substantial clinical problem. There is increasing interest in murine fracture models because they would allow studying molecular mechanisms of healing with the help of specific antibodies and gene-targeted animals. However, until now it has not been possible to reproducibly create non-unions in mice. Thus, the aim of this study was to develop a reliable non-union model in mice. Methods. After creating segmental defects of 0.8 mm and 1.8 mm, mice femora were stabilized with a pin-clip fixation. Additionally, the influence of periosteal resection on the development of non-unions was studied. Histological and radiological healing was analyzed 5, 10, and 15 wk after surgery. Results. After 10 wk all animals showed poor healing with predominantly atrophic non-unions. Whereas the 0.8 mm and the 1.8 mm gap with intact periosteum showed radiologically in 4/6 and 3/6 cases possible healing, only the gap of 1.8 mm with additional periosteal resection resulted in 100% (6/6) non-unions. The non-unions were confirmed also after 15 wk and appeared atrphic with typical histological and radiopeared logical features. These included lack of fracture bridging with abundant fibrous tissue in the gap, absence of callus formation, and rounded bone ends. Of interest, the non-unions were not avascular, but demonstrated a considerable vascularity within the fibrous tissue. Conclusion. Taken together, we herein demonstrate for the first time a reliable non-union model in mice. This allows us to study molecular aspects of non-union formation and analyze different therapeutical strategies in these animals. (C) 2008 Elsevier Inc. All rights reserved.