A multimodal approach to tendon mechanobiology
Achilles tendon ruptures are common and costly, and more than 50% heal unsuccessfully. Tendons respond to mechanical load over time and loading is fundamental for good mechanical performance. However, the regulatory mechanisms are still largely unknown. The main objective of this proposal is to clarify how intact and ruptured healing Achilles tendons are responding to mechanical load. The hypothesis is that the underlying mechanisms can be elucidated through an advanced multimodal approach that combines novel experimental and numerical models across several length scales to clarify the distinct adaptive response of elastic and viscoelastic mechanical behaviour. The proposal combines well-controlled in vivo animal experiments that are uniquely characterized (in situ) to develop and validate novel adaptive computational (in silico) models that can comprehensively predict the spatial and temporal tissue distributions and biomechanical behavior of healthy intact and ruptured healing tendons. On each length scale, experimental mechanical tests are carried out concurrently with 3D/2D high resolution imaging/scattering (in situ), to clarify how the inhomogeneous meso-, micro- and nanostructures behave under loading, in a setup planned to deliver optimal data for development and validation of computational models. 
The interdisciplinary project will deliver high-impact science where the multimodal approach on several length scales could establish new paradigms in tendon biomechanics and mechanobiology. Further, it will lift bioengineering to new levels by unravelling the link between load-controlled molecular mechanisms and viscoelastic mechanical response. It will deliver a novel validated computational framework that the research community may use to propose enhanced solutions for managing tendon injuries. As such, it approaches a well-defined clinical problem from an engineering view, where the PI’s well-received published and ongoing work is the foundation for the idea.