Frontier Engineering: Progression Grant in Modelling complex and partially identified engineering problems. Application to the musculoskeletal system.

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Traditional engineering ignores complex interactions across several space-time scales, which does not fit the context of modelling of biological systems where scales overlap and the inherent complexity of multi-scale interaction cannot be avoided. For this reason, in the previously funded MultiSim project, we established a computational platform for the investigation of musculoskeletal disorders, which we successfully applied to the prediction of the risk of fracture in osteoporotic and osteopenic women, and to the pre-clinical investigation of bone remodelling in animal models to assess the effect of new treatments. Full exploitation of this platform, however, is limited by the fact that most of the MultiSim activities evolved around skeletal health only. MultiSim2 will allow us to expand the focus of our Centre to include an equivalently robust and detailed modelling of the skeletal muscles to predict the effects of pathologies such as sarcopenia or neurodegenerative diseases. To do so, we will develop new approaches for better imaging, characterisation and modelling of the muscles and of their interaction with the skeletal system. In our murine work, we will focus on developing noninvasive longitudinal imaging techniques and computational models to support the reduction and partial replacement of the use of mice in musculoskeletal research. We will measure longitudinal changes in muscle properties by using a micro-magnetic resonance imaging (microMRI) system and advanced image processing to predict tissue changes over time. These measurements will be integrated to a framework of available tools to obtain bone properties at high resolution with in vivo micro-Computed Tomography (microCT) and to co-register all the acquired data in space and time. We will use our human models to predict physiological and pathological changes of muscle volumes and masses, variations in muscle fibres, tendon geometric and elastic properties and changes associated with degeneration in the neuromotor control. The comprehensive assessment of changes in different musculoskeletal tissues (bone, muscles, tendons) over time in both patients and animals will allow us to create a combined experimental and computational framework to better understand and model the effect of diseases and to optimise future treatments.