Abstract

Mechanotransduction is the ability of cells to translate mechanical stimuli into biochemical signals that can ultimately influence gene expression, cell morphology and cell fate. Tenocytes are responsible for tendon mechanical adaptation converting mechanical stimuli imposed during mechanical loading, thus affecting extracellular matrix homeostasis. Since we previously demonstrated that MD-Tissue, an injectable collagen-based medical compound containing swine-derived collagen as the main component, is able to affect tenocyte properties, the aim of this study was to analyze whether the effects triggered by MD-Tissue were based on mechanotransduction-related mechanisms. For this purpose, MD-Tissue was used to coat Petri dishes and cytochalasin B was used to deprive tenocytes of mechanical stimulation mediated by the actin cytoskeleton. Cell morphology, migration, collagen turnover pathways and the expression of key mechanosensors were analyzed by morphological and molecular methods. Our findings confirm that MD-Tissue affects collagen turnover pathways and favors cell migration and show that the MD-Tissue-induced effect represents a mechanical input involving the mechanotransduction machinery. Overall, MD-Tissue, acting as a mechanical scaffold, could represent an effective medical device for a novel therapeutic, regenerative and rehabilitative approach to favor tendon healing in tendinopathies.

Highlights

  • Tendinopathy is a chronic and painful condition affecting tendons, characterized by histological modifications such as hypercellularity, neovascularization, loss of collagen fibril organization, increased proteoglycan and glycosaminoglycan contents and increased non-collagen extracellular matrix components [1,2]

  • We focused our attention on collagen turnover pathways, in order to describe the molecular mechanisms triggered by this medical compound and to understand how it can affect tenocytes’ biological properties to favor tendon homeostasis and repair [19]

  • Since tenocytes act as mechanosensors and it was demonstrated that MD is able to affect collagen turnover pathways and cell migration, the aim of this study was to analyze whether the effects triggered by MD were based on mechanotransduction-related mechanisms

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Summary

Introduction

Tendinopathy is a chronic and painful condition affecting tendons, characterized by histological modifications such as hypercellularity, neovascularization, loss of collagen fibril organization, increased proteoglycan and glycosaminoglycan contents and increased non-collagen extracellular matrix components [1,2]. Cells 2020, 9, 2641 treatment of tendinopathy remains a clinical unmet need, since the available treatments did not show to have a strong efficacy and no long-term benefits were reported [2,4,5]. MD-Tissue (MD) is an injectable collagen-based medical compound containing swine-derived collagen as the main component. Swine collagen has high biocompatibility with human collagen, with a very low risk of adverse effects when used in different medical applications, and it was used to prepare collagen-based skin-like scaffolds [9].

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