A conceptual framework for computational models of Achilles tendon homeostasis

Abstract

Computational modeling of tendon lags the development of computational models for other tissues. A major bottleneck in the development of realistic computational models for Achilles tendon is the absence of detailed conceptual and theoretical models as to how the tissue actually functions. Without the conceptual models to provide a theoretical framework to guide the development and integration of multiscale computational models, modeling of the Achilles tendon to date has tended to be piecemeal and focused on specific mechanical or biochemical issues. In this paper, we present a new conceptual model of Achilles tendon tissue homeostasis, and discuss this model in terms of existing computational models of tendon. This approach has the benefits of structuring the research on relevant computational modeling to date, while allowing us to identify new computational models requiring development. The critically important functional issue for tendon is that it is continually damaged during use and so has to be repaired. From this follows the centrally important issue of homeostasis of the load carrying collagen fibrils within the collagen fibers of the Achilles tendon. Collagen fibrils may be damaged mechanically-by loading, or damaged biochemically-by proteases. Upon reviewing existing computational models within this conceptual framework of the Achilles tendon structure and function, we demonstrate that a great deal of theoretical and experimental research remains to be done before there are reliably predictive multiscale computational model of Achilles tendon in health and disease.

Three dimensional microstructural network of elastin, collagen, and cells in Achilles tendons

“…The fibrils show different tendency of running directions, and fibrils with a same tendency form a secondary unit—fibril bundles. It is widely accepted that collagen fibres are constituted of a group of collagen fibrils in the tendon's hierarchical system, and no endotenon exists between collagen fibres . Therefore, it can be assumed that the definition of collagen fibres in tendon's hierarchical system actually refers to a group of collagen fibril bundles which have similar orientation.…”

Three-dimensional morphology and strain of the Achilles free tendon immediately following eccentric heel drop exercise

“…Because increased tendon longitudinal strain during tensile loading is closely associated with changes in tendon transverse morphology and strain (Obst et al, 2014b;Pokhai et al, 2009;Reeves and Cooper, 2014;Vergari et al, 2011), a similar relationship might be expected for the changes in tendon morphology and strain that occur in response to an exercise bout. In view of the high rate of exerciserelated injuries of the Achilles free tendon and the potential role short-term changes in tendon transverse dimensions could have on the local mechanical and biological environment (Heinemeier and Kjaer, 2011;Shim et al, 2014;Smith et al, 2013), there is a need to better understand the acute effects of exercise on the tendon 3D morphology and strain.…”

“…These changes were not explained by post-exercise differences in muscle activation patterns or torque production, but could reflect non-uniform fatigue or creep of Achilles tendon fascicles, due to differences in mechanical properties and/or tensile loading during eccentric heel drop (Arndt et al, 2011(Arndt et al, , 1998Slane and Thelen, 2014). Irrespective of the cause, acute alterations in the normal biaxial strain could have implications for intra-tendinous force distribution (Haraldsson et al, 2008), fluid flow (Reese et al, 2010;Yin and Elliott, 2004) and tissue homeostasis (Smith et al, 2013) and are therefore relevant in the context of exercise-dependent regional adaptation of Achilles free tendon structure and function. Our findings also suggest that AP diameter may be more responsive to change following exercise, compared with CSA or ML diameter, and support the use of AP diameter to evaluate acute, and possibly chronic, exercisedependent changes in Achilles free tendon transverse morphology (Grigg et al, 2012).…”

High‐resolution study of the 3D collagen fibrillary matrix of Achilles tendons without tissue labelling and dehydrating

“…It is well accepted that collagen forms a hierarchical structure in tendons but the hierarchical structural order has been reported differently by different authors (Benjamin et al, 2008;Liu et al, 2011;Smith et al, 2013). Some scholars claimed that there are collagen fibres with a diameter from 10 to 50 µm in tendons that compose tendon fascicles.…”

“…Collagen (mainly type I collagen) is the most abundant constituent of the extracellular matrix (ECM) of tendons and plays a central role in the tissue's mechanical function (Fratzl et al, 1998;Gelse et al, 2003;Kuijpers et al, 2004;Provenzano & Vanderby, 2006). Thus, the collagen structure has been extensively studied to comprehend the physiology and function of tendons (Harvey et al, 2009;Liu et al, 2011), resulting in establishing nomenclature systems to describe the hierarchical characteristics of the collagen structure in the tendon (Kastelic et al, 1978;Kannus, 2000;Screen et al, 2005;Doroski et al, 2007;Harvey et al, 2009;Smith et al, 2013). However, the nomenclature systems existing in the literature mainly depict the collagen orienting longitudinally in the inner region.…”