The association between mineralised tissue formation and the mechanical local in vivo environment: Time-lapsed quantification of a mouse defect healing model
The association between mineralised tissue formation and the mechanical local in vivo environment: Time-lapsed quantification of a mouse defect healing model
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DOI：
10.1038/s41598-020-57461-5
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发表时间：
2020-01-24
影响因子：
4.6
通讯作者：
Muller, Ralph
中科院分区：
文献类型：
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作者：
Betts, Duncan C. Tourolle ne;Wehrle, Esther;Muller, Ralph
对局部机械刺激如何引导骨折愈合过程的进一步理解有可能提高骨损伤的临床治疗。最近在动物模型中进行的骨缺损临床前研究已经使用横截面数据间接地检查了这一现象。在这项研究中，一个直接的时间推移成像方法被用来调查的局部机械应变之前，在组织规模的矿化组织的形成。目的是测试两个假设：1）在矿化区域中，组织矿化开始之前的局部机械信号较高，以及2）该局部机械信号与缺损中组织的整体机械载荷的大小无关。研究了两组股骨缺损长度为0.85 mm（n = 10）和1.45 mm（n = 9）的小鼠，允许缺损中组织规模应变的不同分布。每周使用体内微型计算机断层扫描（micro-CT）观察矿化组织的再生和（重新）建模，该断层扫描作为解决矿化组织形成区域的基础事实。在基线图像上使用微观有限元分析（micro-FE）确定机械环境。矿化组织的形成显示出与较高机械应变区域的强相关性（曲线下面积：0.91 +/- 0.04，真阳性率：0.85 +/- 0.05），而基于表面的菌株可以正确分类43%的重塑事件。这些研究结果支持我们的假设，显示了直接的本地机械应变和矿化组织的形成之间的关联。
An improved understanding of how local mechanical stimuli guide the fracture healing process has the potential to enhance clinical treatment of bone injury. Recent preclinical studies of bone defect in animal models have used cross-sectional data to examine this phenomenon indirectly. In this study, a direct time-lapsed imaging approach was used to investigate the local mechanical strains that precede the formation of mineralised tissue at the tissue scale. The goal was to test two hypotheses: 1) the local mechanical signal that precedes the onset of tissue mineralisation is higher in areas which mineralise, and 2) this local mechanical signal is independent of the magnitude of global mechanical loading of the tissue in the defect. Two groups of mice with femoral defects of length 0.85 mm (n = 10) and 1.45 mm (n = 9) were studied, allowing for distinct distributions of tissue scale strains in the defects. The regeneration and (re)modelling of mineralised tissue was observed weekly using in vivo micro-computed tomography (micro-CT), which served as a ground truth for resolving areas of mineralised tissue formation. The mechanical environment was determined using micro-finite element analysis (micro-FE) on baseline images. The formation of mineralised tissue showed strong association with areas of higher mechanical strain (area-under-the-curve: 0.91 +/- 0.04, true positive rate: 0.85 +/- 0.05) while surface based strains could correctly classify 43% of remodelling events. These findings support our hypotheses by showing a direct association between the local mechanical strains and the formation of mineralised tissue.