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级的分层组织。虽然胶原结缔组织的结构和力学已经研究了几十年，但对分层组织和材料行为之间的关系缺乏清晰的理解。这可以在很大程度上归因于无法在纳米级、微米级和中尺度之间集成和耦合力学。理论上，这种整合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一个软件框架并系统地研究物理特性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，用于基于开源FEBio软件分析生物力学中的非线性多尺度模型。为了验证这些多尺度建模方法，我们将构建具有明确定义的纳米和微观结构的理想化的多尺度物理代理，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。拟议中的研究将通过提供经过验证的、公开可用的计算工具、模型开发和分层组织多尺度力学验证方法来产生重大影响。我们预计，这项研究的结果和软件框架将在生物学，医学等领域的广泛应用中使用。许多遗传性疾病直接影响胶原蛋白结构和原纤维形成，导致I型胶原蛋白在多个水平上的结构/组织的相对良好表征的改变。拟议的研究是从根本上必要的，使结缔组织的多尺度力学建模从纳米尺度到中尺度。 公共卫生相关性：拟议的研究是从根本上必要的，使结缔组织的多尺度力学建模从纳米尺度到中尺度。对结缔组织中胶原的分级结构和机械功能的更好理解将提供对影响胶原结构的许多疾病和损伤状态的深入了解。

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.