Multiscale models of fibrous interface mechanics

纤维界面力学的多尺度模型

• 批准号: 10601609
• 负责人: Guy M Genin
• 金额: $ 10.13万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10601609
• 关键词: Adhesions; Automobile Driving; Bone Tissue; Connective Tissue; Disease; Failure; Foundations; Friction; Hernia; In Vitro; Injury; Knowledge; Lead; Length; Ligaments; Location; Machine Learning; Mechanics; Mesentery; Minerals; Modeling; Mus; Operative Surgical Procedures; Pain; Pathologic; Pathology; Peritoneal; Pia Mater; Process; Rotator Cuff; Source; Stress; Surface; System; Technology; Tendinopathy; Tendon structure; Testing; Tissue Sample; Tissues; Work; absorption; bone; bone repair; design; disability; experimental study; improved; in vivo; mathematical model; mechanical behavior; molecular dynamics; multi-scale modeling; nano; nanoscale; older patient; parent grant; repaired

PROJECT SUMMARY From parent grant: Interfaces between tissues either transfer load (requiring toughness) or provide a smooth surface (requiring low friction). Fibrous interfaces are very effective at transferring load between tissues, e.g., at connective tissue-bone interfaces (“entheses”), peritoneal-mesentery interfaces, interfaces between layers of the vasculature, and the pia mater. These interfaces require toughness to resist high stresses associated with material mismatches. Surgical repair can lead to smooth interfaces becoming fibrous, (e.g., following hernia surgery) or to tough interfaces becoming weak (e.g., following tendon- and ligament-to-bone repair). In older patients with large rotator cuff repairs, for example, where the desired attachment is not reformed, up to 94% of surgical repairs fail. These challenges arise in part because the features that endow fibrous interfaces with toughness are not known. We therefore propose to develop a comprehensive modeling and experimental approach for studying the factors underlying the transition from tough to weak in a fibrous interface. Our previous work motivates the hypothesis that disorder is a key toughening feature of fibrous attachments. We will focus initially on the example of tendon attaching to bone, in which microscale disorder underlies the ordered macroscale, graded transition between the two tissues, as a foundation for studying the general problem of adhesion throughout the body. We predict that disorder enhances energy absorption by distributing failure processes and energy absorption over larger volumes of tissue. We propose this as a fundamental mechanism by which fibrous interfaces in the body transfer load effectively. We will test these ideas through two aims: (1) Identify and model the mechanisms of fibrous attachment toughening ex vivo. We will model and experimentally validate how disorder across length scales toughens the tendon-to-bone attachment. Hierarchical molecular dynamics-to-continuum models, enriched by machine learning, will be validated in vitro, in systems with nanoscale control of mineral distributions, and ex vivo, in tissue samples of fibrous attachments. (2) Identify and model the loss of fibrous attachment toughness due to pathologic settings in vivo using murine rotator cuff tendinopathy models. In both aims, nano- through milli-scale characterization will be performed to define the mechanisms driving mechanical behavior. We will test the hypothesis that pathology-induced changes at multiple length scales will predict changes in failure mode. These models and experiments will test the hypothesis that energy absorption across hierarchies is a fundamental toughening mechanism by which fibrous interfaces resist injury level loads. Taken together, we believe that these new models of fibrous attachment will enable an understanding of how the order and complexity of fibrous attachments leads to effective attachment of tissues.

项目概要 来自家长资助：组织之间的界面要么转移负荷（需要韧性），要么提供光滑的表面 表面（要求低摩擦）。纤维界面在组织之间转移负载方面非常有效，例如， 结缔组织-骨界面（“附着点”）、腹膜-肠系膜界面、各层之间的界面 脉管系统和软脑膜。这些界面需要韧性来抵抗与 材料不匹配。手术修复可能导致光滑的界面变成纤维状（例如，疝气后 手术）或坚硬的界面变得脆弱（例如，肌腱和韧带与骨骼的修复后）。在较旧的 例如，进行大型肩袖修复的患者，其中所需的附件未进行改造，高达 94% 手术修复失败。这些挑战的出现部分是因为赋予纤维界面的特征 韧性不详。因此，我们建议开发一个全面的建模和实验 研究纤维界面从坚韧到弱化转变的因素的方法。我们之前的 这项工作激发了这样的假设：无序是纤维附着物的一个关键增韧特征。我们将重点 最初以附着在骨头上的肌腱为例，其中微观紊乱是有序的基础 两种组织之间的宏观、分级转变，作为研究一般问题的基础 附着在全身。我们预测无序通过分散失效来增强能量吸收 较大体积组织的过程和能量吸收。我们建议将此作为基本机制 体内的纤维界面通过它有效地传递负荷。我们将通过两个目标来测试这些想法： (1) 识别并模拟离体纤维附着增韧的机制。我们将建模并 通过实验验证长度尺度上的紊乱如何增强肌腱与骨骼的附着。分层的 通过机器学习丰富的分子动力学到连续体模型将在体外系统中得到验证 通过纳米级控制纤维附件组织样本中的矿物质分布和离体。 (2) 识别 并使用小鼠肩袖对体内病理环境导致的纤维附着韧性损失进行建模 肌腱病模型。在这两个目标中，都将进行纳米级到毫米级的表征来定义 驱动机械行为的机制。我们将检验以下假设：病理引起的变化 多个长度尺度将预测失效模式的变化。这些模型和实验将检验假设 跨层次结构的能量吸收是纤维界面的基本增韧机制 抵抗伤害级别的负载。总而言之，我们相信这些新的纤维附着模型将使 了解纤维附着物的顺序和复杂性如何导致组织的有效附着。