SofTMech with MIT and POLIMI (SofTMechMP)

点击翻译按钮获取中文摘要

Soft tissue related diseases (heart, cancer, eyes) are among the leading causes of death worldwide. Despite extensivebiomedical research, a major challenge is a lack of mathematical models that predict soft tissue mechanics acrosssubcellular to whole organ scales during disease progression. Given the tremendous scope, the unmet clinical needs, ourlimited manpower, and the existence of complementary expertise, we seek to forge NEW collaborations with two world-leadingresearch centres: MIT and POLIMI, to embark on two challenging themes that will significantly stretch the initialSofTMech remit: A) Test-based microscale modelling and upscaling, and B) Beyond static hyperelastic material to includeviscoelasticity, nonlinear poroelasticity, tissue damage and healing. Our research will lead to a better understanding of howour bodies work, and this knowledge will be applied to help medical researchers and clinicians in developing new therapiesto minimise the damage caused by disease progression and implants, and to develop more effective treatments.The added value will be a major leap forward in the UK research. It will enable us to model soft tissue damage and healingin many clinical applications, to study the interaction between tissue and implants, and to ensure model reproducibilitythrough in vitro validations. The two underlying themes will provide the key feedback between tissue and cells and theresponse of cells to dynamic local environments. For example, advanced continuum mechanics approaches will shed newlight on the influence of cell adhesion, angiogenesis and stromal cell-tumour interactions in cancer growth and spread, andon wound healing implant insertion that can be tested with in vitro and in vivo systems. Our theoretical framework willprovide insight for the design of new experiments.Our proposal is unique, timely and cost-effectively because advances in micro- and nanotechnology from MIT and POLIMInow enable measurements of sub-cellular, single cell, and cell-ECM dynamics, so that new theories of soft tissuemechanics at the nano- and micro-scales can be tested using in vitro prototypes purposely built for SofTMech. Bridgingthe gaps between models at different scales is beyond the ability of any single centre. SofTMech-MP will cluster the criticalmass to develop novel multiscale models that can be experimentally tested by biological experts within the three world-leadingCentres. SofTMech-MP will endeavour to unlock the chain of events leading from mechanical factors at subcellularnanoscales to cell and tissue level biological responses in healthy and pathological states by building a new mathematicscapacity.Our novel multiscale modelling will lead to new mathematics including new numerical methods, that will be informedand validated by the design and implementation of experiments at the MIT and POLIMI centres. This will be of enormousbenefit in attacking problems involving large deformation poroelasticity, nonlinear viscoelasticity, tissue dissection, stent-relatedtissue damage, and wound healing development. We will construct and analyse data-based models of cellular andsub-cellular mechanics and other responses to dynamic local anisotropic environments, test hypotheses in mechanisticmodels, and scale these up to tissue-level models (evolutionary equations) for growth and remodelling that will take intoaccount the dynamic, inhomogeneous, and anisotropic movement of the tissue. Our models will be simulated in thevarious projects by making use of the scientific computing methodologies, including the new computer-intensive methodsfor learning the parameters of the differential equations directly from noisy measurements of the system, and new methodsfor assessing alternative structures of the differential equations, corresponding to alternative hypotheses about theunderlying biological mechanisms.