SofTMech with MIT and POLIMI (SofTMechMP)

与软组织有关的疾病（心脏、癌症、眼睛）是全世界的主要死亡原因之一。尽管广泛的生物医学研究，一个主要的挑战是缺乏数学模型来预测疾病进展过程中跨亚细胞到整个器官尺度的软组织力学。考虑到巨大的范围，未满足的临床需求，我们有限的人力，以及互补专业知识的存在，我们寻求与两个世界领先的研究中心：麻省理工学院和麻省理工学院建立新的合作关系，开始两个具有挑战性的主题，这将大大扩展最初的softmech范围：A)基于测试的微尺度建模和升级，B)超越静态超弹性材料，包括粘弹性，非线性孔隙弹性，组织损伤和愈合。我们的研究将使我们更好地了解我们的身体是如何工作的，这些知识将被应用于帮助医学研究人员和临床医生开发新的治疗方法，以最大限度地减少疾病进展和植入造成的损害，并开发更有效的治疗方法。附加值将是英国研究的一个重大飞跃。它将使我们能够在许多临床应用中模拟软组织损伤和愈合，研究组织和植入物之间的相互作用，并通过体外验证确保模型的可重复性。这两个基本主题将提供组织和细胞之间的关键反馈以及细胞对动态局部环境的反应。例如，先进的连续介质力学方法将揭示细胞粘附、血管生成和基质细胞-肿瘤相互作用在癌症生长和扩散中的影响，以及可以在体外和体内系统中测试的伤口愈合植入物插入。我们的理论框架将为新实验的设计提供洞见。我们的建议是独特的，及时的和经济有效的，因为来自麻省理工学院和POLIMInow的微纳米技术的进步使亚细胞，单细胞和细胞- ecm动力学的测量成为可能，因此，在纳米和微观尺度上的软组织力学新理论可以使用专门为SofTMech建造的体外原型进行测试。弥合不同尺度模型之间的差距超出了任何一个中心的能力。SofTMech-MP将聚集临界质量来开发新的多尺度模型，这些模型可以由三个世界领先中心的生物专家进行实验测试。SofTMech-MP将通过建立新的数学能力，努力解开从亚细胞纳米尺度的机械因素到健康和病理状态下细胞和组织水平的生物反应的事件链。我们新颖的多尺度建模将导致新的数学，包括新的数值方法，这将被麻省理工学院和波利米中心的实验设计和实施所启发和验证。这将对解决大变形、孔隙弹性、非线性粘弹性、组织剥离、支架相关组织损伤和伤口愈合发展等问题具有巨大的好处。我们将构建和分析基于数据的细胞和亚细胞力学模型，以及对动态局部各向异性环境的其他响应，测试力学模型中的假设，并将这些模型扩展到组织水平模型（进化方程），以考虑组织的动态、不均匀和各向异性运动。我们的模型将通过使用科学计算方法在各种项目中进行模拟，包括用于直接从系统的噪声测量中学习微分方程参数的新的计算机密集型方法，以及用于评估微分方程的替代结构的新方法，对应于关于潜在生物机制的替代假设。

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.