Abstract
Background & Objectives: The objective of this study was to develop a rat model of fracture repair. Fixation of experimental fractures is generally internal {Kirschner wire/intramedullary (IM) nail} or external (single/double plane devices). Internal fixation using the IM-fixated model of a standard closed fracture is well described in rats. However, nail insertion can disrupt fracture site morphology and limit x-ray analysis. We planned to create an externally fixated femoral model, to optimise our outcome measures and facilitate the further investigation of bone healing within the department.
Methods: A simple four pin unilateral external fixator was designed and constructed from four stainless steel pins, secured to a stainless steel plate with nuts. Forty-one female Sprague-Dawley rats, (12–18wks), were used. Following anaesthesia the right femur was exposed and a mid-femoral osteotomy made prior to fixator application. Post-operative x-rays were taken to confirm reduction. Animals were assigned to groups for biomechanical strength testing (BST) or histology. Fifteen animals (fractured and contralateral limbs) were sacrificed at 4, 6 or 8 weeks for BST (four-point bending). Maximum load to failure was recorded and stiffness calculated from the load displacement curve obtained. Both parameters were standardised as a percentage of the contralateral limb. Twenty-five fractured limbs were used for histological analysis at day 4, and 1, 2, 4, 6 or 8 weeks.
Results: Satisfactory reduction was confirmed in all animals post operatively and no complications were noted. Histological assessment at day 4 demonstrated a predominantly lymphocytic inflammatory response within the fracture haematoma. This was replaced with endosteal and periosteal new bone between weeks 1 and 2. Bridging of the fracture gap was seen at week 6. Stiffness and load to failure increased with increasing time. There was a statistically significant improvement in the percentage stiffness (p=0.035) and load to failure (p=0.012) between 4 and 8 weeks.
Conclusion: A simple reproducible externally fixated rat model has been established and characterised by radiography, histology and four point bending. This model has since proven to be of value in the study of the role of lipid lowering and anti-inflammatory drugs as well as cell therapy on fracture repair.
Correspondence should be addressed to Mr Carlos Wigderowitz, Senior Lecturer, University Department of Orthopaedic and Trauma Surgery, Ninewells Hospital and Medical School, Dundee DD1 9SY.
