Mechanobiological modelling of tendons: Review and future opportunities

Abstract

Tendons are adapted to carry large, repeated loads and are clinically important for the maintenance of musculoskeletal health in an increasing, actively ageing population, as well as in elite athletes. Tendons are known to adapt to mechanical loading. Also, their healing and disease processes are highly sensitive to mechanical load. Computational modelling approaches developed to capture this mechanobiological adaptation in tendons and other tissues have successfully addressed many important scientific and clinical issues. The aim of this review is to identify techniques and approaches that could be further developed to address tendon-related problems. Biomechanical models are identified that capture the multi-level aspects of tendon mechanics. Continuum whole tendon models, both phenomenological and microstructurally motivated, are important to estimate forces during locomotion activities. Fibril-level microstructural models are documented that can use these estimated forces to detail local mechanical parameters relevant to cell mechanotransduction. Cell-level models able to predict the response to such parameters are also described. A selection of updatable mechanobiological models is presented. These use mechanical signals, often continuum tissue level, along with rules for tissue change and have been applied successfully in many tissues to predict in vivo and in vitro outcomes. Signals may include scalars derived from the stress or strain tensors, or in poroelasticity also fluid velocity, while adaptation may be represented by changes to elastic modulus, permeability, fibril density or orientation. So far, only simple analytical approaches have been applied to tendon mechanobiology. With the development of sophisticated computational mechanobiological models in parallel with reporting more quantitative data from in vivo or clinical mechanobiological studies, for example, appropriate imaging, biochemical and histological data, this field offers huge potential for future development towards clinical applications.

Tendon injury and repair – A perspective on the basic mechanisms of tendon disease and future clinical therapy

“…How mechanically activated downstream pathways potentially flip the balance between functional remodeling and fibrotic scarring will undoubtedly result in more targeted treatment of tendon disorders. For details on the pathways implicated in tendon mechanotransduction see [17,116,[271][272][273][274]. [57], thus potentially playing a role in age-related tendon disorders.…”

Mimicking the Hierarchical Organization of Natural Collagen: Toward the Development of Ideal Scaffolding Material for Tissue Regeneration

“…However, the precise magnitude, frequency, and duration of stimulation required for normal tendon homeostasis remain unknown. In addition, despite numerous in vivo, in vitro, and ex vivo studies on tendon mechanical properties and the development of prediction models (Galloway et al, 2013;Fang and Lake, 2016;Herod et al, 2016;Thorpe and Screen, 2016;Thompson et al, 2017;Chen et al, 2018;Carniel and Fancello, 2019;Theodossiou and Schiele, 2019), the precise in vivo loading levels required to induce tendon repair are yet unspecified. In this regard, further understanding of the in vivo loading of tendons is vital to understand the mechanobiological stimuli required to induce anabolic or reduce catabolic activity (Lavagnino et al, 2015).…”

In Vitro Cellular Strain Models of Tendon Biology and Tenogenic Differentiation

“…This region is also the point at which the tangent modulus reaches its maximum value. Studies have found that over 4% strain can cause microscopic damage during the sliding of collagen fibrils ( Thompson et al, 2017 ). The failure region of the stress-strain curve demonstrates macroscopic tears associated with strain values over 8–10% ( Butler et al, 2000 ; Thompson et al, 2017 ).…”