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A Simple Critical-sized Femoral Defect Model in Mice

机译:小鼠的简单临界尺寸股骨缺损模型

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摘要

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.
机译:尽管骨骼具有显着的再生能力,但严重的骨骼创伤通常会导致无法正常愈合的损伤。实际上,由于患者的创伤,疾病或年龄的程度,所有肢体骨折的十分之一无法完全治愈。我们改善骨骼再生策略的能力在很大程度上取决于模仿测试动物中严重骨骼创伤的能力,但是大型骨骼病变的产生和稳定在技术上具有挑战性。在大多数情况下,通过建立不会自然愈合的缺陷,可以通过实验模仿严重的长骨创伤。这是通过完全去除大于骨横截面直径1.5倍的骨段来实现的。然后用金属植入物稳定骨骼,以保持骨折边缘的正确方向并允许活动。由于它们的大小和长骨的脆弱性,在小鼠中建立此类病变的能力超出了大多数研究小组的能力。因此,长骨缺损模型仅限于大鼠和较大的动物。尽管如此,小鼠仍具有显着的研究优势,因为它们可以通过基因改造和繁殖成为不会排斥人细胞和组织的免疫受损品系。这里,我们展示了一种使用标准实验室促进小鼠股骨节段性缺损的技术。和兽医设备。通过实践,对于大多数训练有素的兽医和动物研究人员来说,固定装置的制造和手术植入是可行的。使用示例数据,我们还提供了用于模型的骨愈合定量分析的方法。

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