Cellular homeostatic tension and force transmission measured in human engineered tendon

Antonis Giannopoulos,Rene B Svensson,Katja M Heinemeier,Peter Schjerling,Karl E Kadler,David F Holmes,Michael Kjaer,S Peter Magnusson

doi:10.1016/j.jbiomech.2018.07.032

Abstract

Tendons transmit contractile muscular force to bone to produce movement, and it is believed cells can generate endogenous forces on the extracellular matrix to maintain tissue homeostasis. However, little is known about the direct mechanical measurement of cell-matrix interaction in cell-generated human tendon constructs. In this study we examined if cell-generated force could be detected and quantified in engineered human tendon constructs, and if glycosaminoglycans (GAGs) contribute to tendon force transmission. Following de-tensioning of the tendon constructs it was possible to quantify an endogenous re-tensioning. Further, it was demonstrated that the endogenous re-tensioning response was markedly blunted after interference with the cytoskeleton (inhibiting non-muscle myosin-dependent cell contraction by blebbistatin), which confirmed that re-tensioning was cell generated. When the constructs were elongated and held at a constant length a stress relaxation response was quantified, and removing 27% of the GAG content of tendon did not alter the relaxation behavior, which indicates that GAGs do not play a meaningful role in force transmission within this system.

Highlights

The chief function of tendon is to transmit contractile muscular force to bone to produce movement
It has been shown that placing sizeable repetitive loads on the tendon may influence numerous cell responses (Spiesz et al, 2015), tissue composition (Langberg et al, 1999) and mechanical properties of the tendon (Hansen et al, 2003), which indicates that tendon tissue is mechanoresponsive the precise pathway is unknown (Harris et al, 1980; Wang et al, 2012)
While the tendon can impart forces on the cell, it is possible for cell to generate endogenous forces on the extracellular matrix (ECM) (Eastwood et al, 1994; Kolodney and Wysolmerski, 1992), which allows for a fine-tuned dynamic interaction between the cell

Summary

Introduction

The chief function of tendon is to transmit contractile muscular force to bone to produce movement. It has been shown that placing sizeable repetitive loads on the tendon may influence numerous cell responses (Spiesz et al, 2015), tissue composition (Langberg et al, 1999) and mechanical properties of the tendon (Hansen et al, 2003), which indicates that tendon tissue is mechanoresponsive the precise pathway is unknown (Harris et al, 1980; Wang et al, 2012). Cellgenerated scaffolds comprise a mixture of ECM components that more likely resemble that of the in vivo situation compared to the aforementioned models Such cell-derived tendon construct have been developed using both animal (Kapacee et al, 2008) and human cells (Bayer et al, 2010), with similar composition (Kapacee et al, 2008) and mechanical properties (Herchenhan et al, 2013) to embryonic tendon tissue (Kalson et al, 2010).

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