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The effect of mechanical stimulation on bone fracture healing: Changes in callus morphology and mesenchymal stem cell homing.

机译：机械刺激对骨折愈合的影响：愈伤组织形态和间充质干细胞归巢的变化。

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摘要

This dissertation examines how the timing of an applied strain influences callus morphology during bone fracture repair, and how this load effects the migration of systemically delivered mesenchymal stem cells (MSCs) to the fracture site. Six-month-old, male, Sprague-Dawley rats underwent a 2mm segmental osteotomy in the mid-diaphysis of each femur. A two-piece external fixator with locking plate was fixed to each femur, an osteotomy created with an oscillating saw, and the surrounding tissues closed. Systemic injections of green fluorescent protein (GFP) labeled MSCs were performed via the tail vein on the first loading day. Axial mechanical stimulation occurred for five consecutive days at 0, 3, 10, or 24 days post-operative at a magnitude of ±8% strain and a rate of 0.313 Hz for 510 cycles. Rats were euthanized 10, 24, or 48 days post-op.;Through a micro-CT analysis, mineralization was found to be increased in animals that underwent the applied displacement at day ten when compared to the other groups. Histology showed that by day 48, these animals had almost no cartilage remaining, indicating advanced remodeling in comparison to other groups. The animals stimulated at day three showed the opposite trends, with less mineralization and larger, less remodeled calluses by day 48.;Planar gamma imaging of 111indium tagged MSCs showed that injected cells migrate from the lungs and liver, and a certain percentage of them are available to the limbs. Axial displacement created some difference in MSC migration to the limbs, but these disappeared by day three. As analyzed by immunohistochemistry, there were significant numbers of MSCs in the marrow spaces by day 48, and a qualitative analysis suggests that stimulation may encourage the cell to preferentially migrate.;A polymerase chain reaction (PCR) array examined the genetic expression of 80 genes in the fracture gap tissue implicated in migration of MSC migration. It showed that the expression of many different genetic factors is influenced by mechanical stimulation. This effect also appears to not just be localized, but can be seen systemically as well.;Overall, the timing of displacement had a significant effect on fracture healing, both locally and systemically.
机译：本论文研究了施加的应变的时机如何在骨折修复过程中影响愈伤组织的形态，以及该负荷如何影响全身递送的间充质干细胞（MSCs）向骨折部位的迁移。六个月大的雄性Sprague-Dawley大鼠在每个股骨的中骨干处进行了2mm的节段截骨术。将带有锁定板的两件式外固定器固定在每个股骨上，用摆动的锯进行切骨术，并闭合周围组织。在第一个加载日通过尾静脉全身注射绿色荧光蛋白（GFP）标记的MSC。轴向机械刺激在术后0、3、10或24天连续五天，以±8％的应变和0.313 Hz的频率连续510个周期。术后10天，24天或48天对大鼠实施安乐死；通过显微CT分析，与其他组相比，在第10天进行了置换的动物中矿化作用增加。组织学表明，到第48天，这些动物几乎没有剩余软骨，这表明与其他组相比，它们的重塑程度更高。在第3天受刺激的动物表现出相反的趋势，到第48天具有较少的矿化和较大的重塑愈伤组织； 111铟标记的MSC的平面伽马成像显示，注射的细胞从肺和肝中迁移出来，其中一定比例是可供四肢使用。轴向移位在MSC向四肢的迁移中产生了一些差异，但是这些在第三天就消失了。通过免疫组织化学分析，到第48天时，骨髓间隙中存在大量MSC，定性分析表明刺激可能会鼓励细胞优先迁移。;聚合酶链反应（PCR）阵列检查了80个基因的基因表达在骨折缝隙组织中牵涉到MSC的迁移。结果表明，许多不同的遗传因素的表达受机械刺激的影响。这种作用似乎不仅是局部的，而且在系统上也可以看到。总的来说，移位的时机对局部和全身的骨折愈合都有重要影响。

著录项

  • 作者

    Weaver, Aaron Seth.;

  • 作者单位

    University of Michigan.;

  • 授予单位 University of Michigan.;
  • 学科 Biology Cell.;Engineering Biomedical.;Engineering Mechanical.
  • 学位 Ph.D.
  • 年度 2008
  • 页码 103 p.
  • 总页数 103
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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