Williams Justin N, Li Yong, Valiya Kambrath Anuradha, Sankar Uma
Department of Anatomy and Cell Biology, Indiana University School of Medicine.
Department of Anatomy and Cell Biology, Indiana University School of Medicine;
J Vis Exp. 2018 Aug 16(138):58122. doi: 10.3791/58122.
Bone fractures impose a tremendous socio-economic burden on patients, in addition to significantly affecting their quality of life. Therapeutic strategies that promote efficient bone healing are non-existent and in high demand. Effective and reproducible animal models of fractures healing are needed to understand the complex biological processes associated with bone regeneration. Many animal models of fracture healing have been generated over the years; however, murine fracture models have recently emerged as powerful tools to study bone healing. A variety of open and closed models have been developed, but the closed femoral fracture model stands out as a simple method for generating rapid and reproducible results in a physiologically relevant manner. The goal of this surgical protocol is to generate unilateral closed femoral fractures in mice and facilitate a post-fracture stabilization of the femur by inserting an intramedullary steel rod. Although devices such as a nail or a screw offer greater axial and rotational stability, the use of an intramedullary rod provides a sufficient stabilization for consistent healing outcomes without producing new defects in the bone tissue or damaging nearby soft tissue. Radiographic imaging is used to monitor the progression of callus formation, bony union, and subsequent remodeling of the bony callus. Bone healing outcomes are typically associated with the strength of the healed bone and measured with torsional testing. Still, understanding the early cellular and molecular events associated with fracture repair is critical in the study of bone tissue regeneration. The closed femoral fracture model in mice with intramedullary fixation serves as an attractive platform to study bone fracture healing and evaluate therapeutic strategies to accelerate healing.
骨折除了会严重影响患者的生活质量外，还会给他们带来巨大的社会经济负担。目前尚不存在能促进有效骨愈合的治疗策略，对此有迫切需求。为了了解与骨再生相关的复杂生物学过程，需要有效且可重复的骨折愈合动物模型。多年来已经建立了许多骨折愈合动物模型；然而，小鼠骨折模型最近已成为研究骨愈合的有力工具。已经开发了多种开放性和闭合性模型，但闭合性股骨骨折模型作为一种简单的方法脱颖而出，能够以生理相关的方式快速产生可重复的结果。本手术方案的目的是在小鼠中造成单侧闭合性股骨骨折，并通过插入髓内钢棒促进骨折后股骨的稳定。虽然诸如髓内钉或螺丝钉等装置能提供更大的轴向和旋转稳定性，但使用髓内棒可提供足够的稳定性以实现一致的愈合结果，且不会在骨组织中产生新的缺损或损伤附近的软组织。通过放射成像来监测骨痂形成、骨愈合以及随后骨痂重塑的进展。骨愈合结果通常与愈合骨的强度相关，并通过扭转试验进行测量。尽管如此，了解与骨折修复相关的早期细胞和分子事件在骨组织再生研究中至关重要。采用髓内固定的小鼠闭合性股骨骨折模型是研究骨折愈合和评估加速愈合治疗策略的一个有吸引力的平台。
