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Graft alignment impacts the regenerative response of skeletal muscle after volumetric muscle loss in a rat model

机译：移植物对准会影响大鼠模型体积肌肉损失后骨骼肌的再生响应

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摘要

A key event in the etiology of volumetric muscle loss (VML) injury is the bulk loss of structural cues provided by the underlying extracellular matrix (ECM). To re-establish the lost cues, there is broad consensus within the literature supporting the utilization of implantable scaffolding. However, while scaffold based regenerative medicine strategies have shown potential, there remains a significant amount of outcome variability observed across the field. We suggest that an overlooked source of outcome variability is differences in scaffolding architecture. The goal of this study was to test the hypothesis that implant alignment has a significant impact on genotypic and phenotypic outcomes following the repair of VML injuries. Using a rat VML model, outcomes across three autograft implant treatment groups (aligned implants, 45 misaligned, and 90 misaligned) and two recovery time points (2 weeks and 12 weeks) were examined (n = 6-8/group). At 2 weeks post-repair there were no significant differences in muscle mass and torque recovery between the treatment groups, however we did observe a significant upregulation of MyoD (2.5 fold increase) and Pax? (2 fold increase) gene expression as well as the presence of immature myofibers at the implant site for those animals repaired with aligned autografts. By 12 weeks post-repair, functional and structural differences between the treatment groups could be detected. Aligned autografts had significantly greater mass and torque recovery (77 10% of normal) when compared to 45 and 90 misaligned autografts (64 10% and 61 11%, respectively). Examination of tissue structure revealed extensive fibrosis and a significant increase in non-contractile tissue area fraction for only those animals treated using misaligned autografts. When taken together, the results suggest that implant graft orientation has a significant impact on in-vivo outcomes and indicate that the effect of graft alignment on muscle phenotype may be mediated through genotypic changes to myogenesis and fibrosis at the site of injury and repair.
机译：体积肌损伤（VML）损伤的病因中的关键事件是潜在的细胞外基质（ECM）提供的结构提示的散装损失。要重新建立丢失的线索，在有助于利用植入脚手架的文献中存在广泛的共识。然而，虽然基于支架的再生医学策略表明了潜力，但在整个领域中仍然存在大量的结果可变性。我们建议忽视的结果变异性是脚手架架构的差异。本研究的目标是测试植入对准对基因型和表型结果产生重大影响的假设，在修复VML损伤后。使用大鼠VML模型，检查三个自体移植植入物处理组的结果（对齐植入物，45个错位，90个未对准）和两个恢复时间点（2周和12周）（n = 6-8 /组）。在修复后2周，治疗组之间的肌肉质量和扭矩恢复没有显着差异，但我们确实观察了Myod的显着上调（2.5倍）和Pax？ （2倍增加）基因表达以及在植入部位的那些用对齐的自体移植物修复的那些动物的植入部位存在未成熟的肌泡。在修复后12周，可以检测治疗组之间的功能性和结构差异。与45和90个未对准的自体移植相比，对齐的自体移植物的质量和扭矩恢复明显更大，扭矩恢复（正常的77％）（分别为640％和61％）。组织结构的检查揭示了广泛的纤维化和仅使用未对准的自体移植物治疗的动物的非收缩组织面积分数显着增加。当占据时，结果表明，植入移植方向对体内结果产生重大影响，并表明接枝对准对肌肉表型的影响可以通过基因型变化对损伤部位的肌生成和纤维化的基因型变化来介导。

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  • 来源
    《Acta biomaterialia》 |2020年第2020期|共12页
  • 作者

    Kim John; Kasukonis Ben; Roberts Kevin; Dunlap Grady; Brown Lemuel; Washington Tyrone; Wolchok Jeffrey;

  • 作者单位

    Univ Arkansas Coll Engn Dept Biomed Engn Fayetteville AR 72701 USA;

    Univ Arkansas Coll Engn Dept Biomed Engn Fayetteville AR 72701 USA;

    Univ Arkansas Coll Engn Dept Biomed Engn Fayetteville AR 72701 USA;

    Univ Arkansas Coll Engn Dept Biomed Engn Fayetteville AR 72701 USA;

    Univ Arkansas Coll Educ &

    Hlth Profess Dept Hlth Human Performance &

    Recreat Fayetteville AR;

    Univ Arkansas Coll Educ &

    Hlth Profess Dept Hlth Human Performance &

    Recreat Fayetteville AR;

    Univ Arkansas Coll Engn Dept Biomed Engn Fayetteville AR 72701 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 普通生物学;
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