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The mechanobiology of tendon fibroblasts under static and uniaxial cyclic load in a 3D tissue engineered model mimicking native extracellular matrix.
Journal of Tissue Engineering and Regenerative Medicine ( IF 3.3 ) Pub Date : 2019-12-03 , DOI: 10.1002/term.2975
Prasad Sawadkar 1 , Darren Player 1 , Laurent Bozec 2 , Vivek Mudera 1
Affiliation  

Tendon mechanobiology plays a vital role in tendon repair and regeneration; however, this mechanism is currently poorly understood. We tested the role of different mechanical loads on extracellular matrix (ECM) remodelling gene expression and the morphology of tendon fibroblasts in collagen hydrogels, designed to mimic native tissue. Hydrogels were subjected to precise static or uniaxial loading patterns of known magnitudes and sampled to analyse gene expression of known mechano-responsive ECM-associated genes (Collagen I, Collagen III, Tenomodulin, and TGF-β). Tendon fibroblast cytomechanics was studied under load by using a tension culture force monitor, with immunofluorescence and immunohistological staining used to examine cell morphology. Tendon fibroblasts subjected to cyclic load showed that endogenous matrix tension was maintained, with significant concomitant upregulation of ECM remodelling genes, Collagen I, Collagen III, Tenomodulin, and TGF-β when compared with static load and control samples. These data indicate that tendon fibroblasts acutely adapt to the mechanical forces placed upon them, transmitting forces across the ECM without losing mechanical dynamism. This model demonstrates cell-material (ECM) interaction and remodelling in preclinical a platform, which can be used as a screening tool to understand tendon regeneration.

中文翻译:

在静态和单轴循环载荷下模拟天然细胞外基质的3D组织工程模型中,肌腱成纤维细胞的力学生物学。

肌腱力学在肌腱的修复和再生中起着至关重要的作用。但是,这种机制目前知之甚少。我们测试了不同机械负荷对胶原蛋白水凝胶中细胞外基质(ECM)重塑基因表达和肌腱成纤维细胞形态的作用,旨在模拟天然组织。将水凝胶置于已知大小的精确静态或单轴加载模式下,并取样以分析已知与机械响应的ECM相关基因(胶原蛋白I,胶原蛋白III,Tenomodulin和TGF-β)的基因表达。通过使用张力培养力监测仪在负荷下研究肌腱成纤维细胞的细胞力学,并用免疫荧光和免疫组织学染色检查细胞形态。肌腱成纤维细胞承受循环载荷后,内源性基质张力得以维持,与静态负载和对照样品相比,ECM重塑基因,I型胶原,III型胶原,Tenomodulin和TGF-β显着伴随上调。这些数据表明,肌腱成纤维细胞能迅速适应施加在其上的机械力,从而在不失去机械动力的情况下将力传递给整个ECM。该模型演示了临床前平台中的细胞-材料(ECM)相互作用和重塑,可将其用作筛选工具以了解肌腱再生。
更新日期:2019-12-03
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