AO Research Institute Davos, Clavandelerstrasse 8, 7270, Davos Platz, Switzerland.
Department of Surgery and Trauma Surgery and NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands.
Arch Orthop Trauma Surg. 2019 Dec;139(12):1743-1753. doi: 10.1007/s00402-019-03255-y. Epub 2019 Aug 9.
Delayed union and nonunion development remain a major clinical problematic complication during fracture healing, with partially unclear pathophysiology. Incidences range from 5 to 40% in high-risk patients, such as patients with periosteal damage. The periosteum is essential in adequate fracture healing, especially during soft callus formation. In this study, we hypothesize that inducing periosteal damage in a murine bone healing model will result in a novel delayed union model.
A mid-shaft femoral non-critically sized osteotomy was created in skeletally mature C57BL/6 mice and stabilized with a bridging plate. In half of the mice, a thin band of periosteum adjacent to the osteotomy was cauterized. Over 42 days of healing, radiographic, biomechanical, micro-computed tomography and histological analysis was performed to assess the degree of fracture healing.
Analysis showed complete secondary fracture healing in the control group without periosteal injury. Whereas the periosteal injury group demonstrated less than half as much maximum callus volume (p < 0.05) and bridging, recovery of stiffness and temporal expression of callus growth and remodelling was delayed by 7-15 days.
This paper introduces a novel mouse model of delayed union without a critically sized defect and with standardized biomechanical conditions, which enables further investigation into the molecular biological, biomechanical, and biochemical processes involved in (delayed) fracture healing and nonunion development. This model provides a continuum between normal fracture healing and the development of nonunions.
在骨折愈合过程中，延迟愈合和不愈合仍然是一个主要的临床问题并发症，其部分病理生理学机制尚不清楚。在高风险患者（如骨膜损伤患者）中，发病率范围为 5%至 40%。骨膜对于充分的骨折愈合至关重要，特别是在软骨痂形成过程中。在这项研究中，我们假设在鼠骨愈合模型中诱导骨膜损伤将导致新的延迟愈合模型。
在骨骼成熟的 C57BL/6 小鼠的股骨干中部非关键大小的骨切开处创建骨切开，并使用桥接板稳定。在一半的小鼠中，在骨切开处附近的薄骨膜带被烧灼。在 42 天的愈合过程中，进行放射照相、生物力学、微计算机断层扫描和组织学分析，以评估骨折愈合的程度。
分析表明，对照组在没有骨膜损伤的情况下完全实现了二次骨折愈合。而骨膜损伤组的最大骨痂体积不到对照组的一半（p<0.05），并且刚度的恢复以及骨痂生长和重塑的时间表达延迟了 7-15 天。
本文介绍了一种新型的鼠延迟愈合模型，没有临界大小的缺陷和标准化的生物力学条件，这使得可以进一步研究涉及（延迟）骨折愈合和不愈合发展的分子生物学、生物力学和生化过程。该模型提供了正常骨折愈合和不愈合发展之间的连续体。
