A Simple Critical-sized Femoral Defect Model in Mice

Bret H. Clough; Matthew R. McCarley; Carl A. Gregory

doi:10.3791/52368

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Method Article

A Simple Critical-sized Femoral Defect Model in Mice

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DOI:

10.3791/52368

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March 15th, 2015

Bret H. Clough¹ , Matthew R. McCarley² , Carl A. Gregory¹^,³

¹Institute for Regenerative Medicine at Scott & White Hospital, Texas A&M Health Science Center, ²Department of Orthopedic Surgery, University of Texas Medical Branch, ³Molecular and Cellular Medicine, Texas A&M Health Science Center

Summary

Animal models are frequently employed to mimic serious bone injury in biomedical research. Due to their small size, establishment of stabilized bone lesions in mice are beyond the capabilities of most research groups. Herein, we describe a simple method for establishing and analyzing experimental femoral defects in mice.

Abstract

While bone has a remarkable capacity for regeneration, serious bone trauma often results in damage that does not properly heal. In fact, one tenth of all limb bone fractures fail to heal completely due to the extent of the trauma, disease, or age of the patient. Our ability to improve bone regenerative strategies is critically dependent on the ability to mimic serious bone trauma in test animals, but the generation and stabilization of large bone lesions is technically challenging. In most cases, serious long bone trauma is mimicked experimentally by establishing a defect that will not naturally heal. This is achieved by complete removal of a bone segment that is larger than 1.5 times the diameter of the bone cross-section. The bone is then stabilized with a metal implant to maintain proper orientation of the fracture edges and allow for mobility.

Due to their small size and the fragility of their long bones, establishment of such lesions in mice are beyond the capabilities of most research groups. As such, long bone defect models are confined to rats and larger animals. Nevertheless, mice afford significant research advantages in that they can be genetically modified and bred as immune-compromised strains that do not reject human cells and tissue.

Herein, we demonstrate a technique that facilitates the generation of a segmental defect in mouse femora using standard laboratory and veterinary equipment. With practice, fabrication of the fixation device and surgical implantation is feasible for the majority of trained veterinarians and animal research personnel. Using example data, we also provide methodologies for the quantitative analysis of bone healing for the model.

Introduction

It is estimated that half of the US population experience a fracture by the age of 65¹. For those patients with fractures treated surgically, 500,000 procedures involve the use of a bone graft² and this number is expected to rise with an increasingly aging population³. Although bone is one of the few organs that has the capacity to completely heal without scarring, there are instances where the process fails^3,4. Depending on the circumstances and quality of treatment, 2-30% of long bone fractures fail, resulting in non-union^3,5. While there remains some debate on the definition, pseudoarthrosis, critical-sized or ....