Computational Framework for Multiscale Mechanics of Connective Tissues

描述（由申请人提供）：大多数结缔组织主要由胶原蛋白组成，并表现出从纳米到毫米尺度的分层组织。虽然胶原结缔组织的结构和力学已经研究了几十年，但对等级组织和材料行为之间的关系仍缺乏清晰的认识。这在很大程度上归因于无法整合和耦合纳米尺度、微尺度和中尺度之间的力学。理论上，这种集成可以使用计算均匀化来完成。本研究的总体目标是通过开发软件框架和系统地研究物理特征和假设对算法预测的影响，实现分层结缔组织的多尺度力学建模。作为研究的一部分，我们将开发基于有限元（FE）的算法和软件框架，用于分析生物力学中的非线性，多尺度模型，基于开源的FEBio软件。为了验证这些多尺度建模方法，我们将构建具有良好定义的纳米和微观结构的理想的多尺度物理替代品，并在宏观和微观尺度上同时进行材料表征。这些信息将用于开发和验证物理替代品的参数化、多尺度有限元模型。拟议的研究将通过为分层组织的多尺度力学提供经过验证的、公开可用的计算工具、模型开发和验证方法，产生重大影响。我们预计，这项研究的结果和软件框架将在生物学、医学等领域广泛应用。许多遗传性疾病直接影响胶原结构和纤维形成，导致I型胶原在多个水平上的结构/组织发生相对明确的改变。所提出的研究对于实现从纳米尺度到中尺度的结缔组织的多尺度力学建模是必不可少的。

DESCRIPTION (provided by applicant): Most connective tissues are composed primarily of collagen and exhibit hierarchical organization from the nanometer to the millimeter scale. Although the structure and mechanics of collagenous connective tissues have been studied for decades, a clear understanding of the relationships between hierarchical organization and material behavior is severely lacking. This can be attributed in large part to an inability to integrate and couple mechanics between the nanoscale, microscale and mesoscale. In theory, this integration can be accomplished using computational homogenization. The overall aim of this research is to enable multiscale mechanical modeling of hierarchical connective tissues, by developing a software framework and systematically investigating the influence of physical characteristics and assumptions on the predictions from the algorithms. As part of the research, we will develop finite element (FE) based algorithmic and software framework for analysis of nonlinear, multiscale models in biomechanics, based on the open-source FEBio software. To validate these approaches to multiscale modeling, we will construct idealized, multiscale physical surrogates with well-defined nano- and microstructure and perform simultaneous material characterization at the macro- and microscale. This information will be used to develop and validate parametric, multiscale FE models of the physical surrogates. The proposed research will create a significant impact by providing verified, publicly available computational tools, model development and validation methodologies for multiscale mechanics of hierarchical tissues. We anticipate that the results of this research and the software framework will be utilized across a broad range of applications in biology, medicine and beyond. Many heritable diseases directly affect collagen structure and fibrillogenesis, causing relatively well-characterized alterations in structure/organization of type I collagen at multiple levels. The proposed research is fundamentally necessary to enable multiscale mechanical modeling of connective tissues from the nanoscale to the mesoscale. PUBLIC HEALTH RELEVANCE: The proposed research is fundamentally necessary to enable multiscale mechanical modeling of connective tissues from the nanoscale to the mesoscale. An improved understanding of the hierarchical structure and mechanical function of collagen in connective tissues will provide insight into the many disease and injury states that affect collagen structure.