Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany; Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany.
Institute for Clinical and Experimental Surgery, Saarland University, 66421 Homburg/Saar, Germany.
Bone. 2022 Sep;162:116475. doi: 10.1016/j.bone.2022.116475. Epub 2022 Jun 23.
Despite growing knowledge about the mechanisms of fracture healing, non-union formation still represents a major complication in trauma and orthopedic surgery. Non-union models in mice gain increasing interest, because they allow investigating the molecular and cellular mechanisms of failed fracture healing. These models often use segmental defects to achieve non-union formation. Alternatively, failed fracture healing can be induced by transverse fractures with additional periosteal injury. The present study systematically compared the reliability of these two approaches to serve as non-union model. A 0.6 mm K-wire was inserted into the femora of CD-1 mice in a retrograde fashion and a closed transverse femoral fracture was created. Subsequently, the fracture site was exposed and the periosteum was cauterized. This approach was compared with a well-established non-union model involving the pin-clip fixation of a 1.8 mm segmental defect. The callus tissue was analyzed by means of radiography, biomechanics, histology and Western blotting. At 10 weeks after surgery 10 out of 12 femora (83.3 %) of the K-wire group showed a non-union formation. The pin-clip model resulted in 100 % non-union formation. The K-wire group showed increased bone formation, osteoclast activity and bending stiffness when compared to the group with pin-clip fixation. This was associated with a higher expression of bone formation markers. However, the number of CD31-positive microvessels was reduced in the K-wire group, indicating an impaired angiogenic capacity after periosteal cauterization. These findings suggest that the pin-clip model is more reliable for the study of non-union formation in mice. The K-wire model including periosteal injury by cauterization however, may be particularly applied in preclinical studies which explore the effects of damaged periosteum and reduced angiogenic capacity to trauma-induced fractures.
尽管人们对骨折愈合机制的了解日益增加，但骨不连的形成仍然是创伤和骨科手术中的一个主要并发症。在小鼠中建立骨不连模型越来越受到关注，因为它们可以研究骨折愈合失败的分子和细胞机制。这些模型通常使用节段性缺损来实现骨不连的形成。或者，可以通过横向骨折伴骨膜损伤来诱导骨折愈合失败。本研究系统比较了这两种方法作为骨不连模型的可靠性。将 0.6mm 的 K 型钉逆行插入 CD-1 小鼠的股骨中，造成闭合性股骨横向骨折。随后，暴露骨折部位并灼烧骨膜。将这种方法与一种成熟的骨不连模型进行比较，该模型涉及使用销钉夹固定 1.8mm 的节段性缺损。通过 X 射线、生物力学、组织学和 Western blot 分析骨痂组织。手术后 10 周，12 只股骨中有 10 只（83.3%）K 型钉组出现骨不连形成。销钉夹模型导致 100%的骨不连形成。与使用销钉夹固定的组相比，K 型钉组的骨形成增加，破骨细胞活性和弯曲刚度增加。这与骨形成标志物表达增加有关。然而，K 型钉组的 CD31 阳性微血管数量减少，表明骨膜灼烧后血管生成能力受损。这些发现表明，销钉夹模型更适合研究小鼠的骨不连形成。然而，包括骨膜灼烧损伤的 K 型钉模型可能特别适用于探索受损骨膜和减少的血管生成能力对创伤性骨折的影响的临床前研究。
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