The mechanobiology of tendon fibroblasts under static and uniaxial cyclic load in a 3D tissue engineered model mimicking native ECM

Prasad Sawadkar, Darren Player, Laurent Bozec, Vivek Mudera
Journal of Tissue Engineering and Regenerative Medicine 2019 October 17
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 extra-cellular 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 (COL I, COL III, Tenomodulin and TGF-β). Tendon fibroblast cytomechanics was studied under load by using a tension culture force monitor (t-CFM), with immunofluorescence and immunohistological staining used to examine cell morphology. Tendon fibroblasts subjected to cyclic load showed endogenous matrix tension was maintained, with significant concomitant upregulation of ECM remodelling genes, COL I, COL III, Tenomodulin, and TGF-b when compared to 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 pre-clinical a platform, which can be used as a screening tool to understand tendon regeneration.

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