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SofTMech with MIT and POLIMI (SofTMechMP)

SofTMech 与 MIT 和 POLIMI (SofTMechMP)

基本信息

批准号：
EP/S030875/1
负责人：
XiaoYu Luo
金额：
$ 203.81万
依托单位：
University of Glasgow
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2020
资助国家：
英国
起止时间：
2020 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FS030875%2F1
关键词：
SofTMech MIT POLIMI SofTMechMP

项目摘要

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.

与软组织相关的疾病（心脏病、癌症、眼科）是全世界死亡的主要原因之一。尽管进行了广泛的生物医学研究，但一个主要挑战是缺乏数学模型来预测疾病进展期间跨亚细胞到整个器官尺度的软组织力学。鉴于巨大的范围，未满足的临床需求，我们有限的人力资源，以及互补的专业知识的存在，我们寻求与两个世界领先的研究中心建立新的合作关系：麻省理工学院和波利米，着手两个具有挑战性的主题，这将大大扩展初始SoftTM技术的职权范围：A）基于测试的微尺度建模和放大，以及B）超越静态超弹性材料以包括粘弹性、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物造成的损害，并开发更有效的治疗方法。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为细胞粘附、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伤口愈合植入物插入提供新的思路，这些都可以用体外和体内系统进行测试。我们的理论框架将为新实验的设计提供见解。我们的建议是独特的，及时的和具有成本效益的，因为来自MIT和POLIMI的微米和纳米技术的进步现在使亚细胞，单细胞和细胞ECM动力学的测量成为可能，因此纳米和微米尺度的软组织力学的新理论可以使用专门为SofTMech构建的体外原型进行测试。弥合不同规模模型之间的差距超出了任何单一中心的能力。SoftMech-MP将对临界质量进行聚类，以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将致力于通过建立一个新的生物学能力来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，这些方法将通过MIT和POLIMI中心的实验设计和实施来提供信息和验证。这对于解决大变形多孔弹性、非线性粘弹性、组织剥离、支架相关组织损伤和伤口愈合等问题具有重要意义。我们将构建和分析基于数据的细胞和亚细胞力学模型和其他对动态局部各向异性环境的响应，测试力学模型中的假设，并将其扩展到组织级模型（进化方程），用于生长和重塑，将考虑组织的动态，不均匀和各向异性运动。我们的模型将通过利用科学计算方法在各种项目中进行模拟，包括直接从系统的噪声测量中学习微分方程参数的新计算机密集型方法，以及评估微分方程替代结构的新方法，对应于有关潜在生物机制的替代假设。