Mechanobiological modelling of tendons: Review and future opportunities.

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.