Multiscale models of fibrous interface mechanics

纤维界面力学的多尺度模型

• 批准号: 10678848
• 负责人: Guy M Genin
• 金额: $ 46.73万
• 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/10678848
• 关键词: Adhesions; Adhesives; Animal Model; Automobile Driving; Biological Models; Bone Tissue; Botulinum Toxin Type A; Brain; Characteristics; Collagen; Collagen Diseases; Collagen Fiber; Connective Tissue; Disease; Endowment; Environment; Failure; Fiber; Foundations; Friction; Hernia; In Vitro; Injury; Intra-abdominal; Knowledge; Laparotomy; Length; Ligaments; Location; Machine Learning; Mechanics; Meniscus structure of joint; Mesentery; Minerals; Modeling; Modification; Mus; Musculoskeletal; Nature; Nervous System; Operative Surgical Procedures; Pain; Paralysed; Pathologic; Pathology; Patients; Peritoneal; Physiological; Pia Mater; Process; Rotator Cuff; Running; Skin; Slide; Source; Specimen; Stress; Structure; Surface; System; Technology; Tendinopathy; Tendon structure; Testing; Tissue Sample; Tissues; Work; absorption; behavior prediction; bone; bone repair; cranium; crosslink; design; disability; experimental study; improved; in vivo; mathematical model; mechanical behavior; millimeter; molecular dynamics; multi-scale modeling; nano; nanocrystal; nanoscale; older patient; repaired; treadmill

PROJECT SUMMARY 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 global 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.

项目摘要 在组织之间接口转移负载（需要韧性）或提供光滑的表面 （需要低摩擦）。纤维界面非常有效地在组织之间传递载荷，例如 在结缔组织 - 骨界面（“恩特孔”），腹膜 - 渗透界面，界面 在脉管系统的层和PIA材料之间。这些接口需要韧性才能抵抗 与材料不匹配相关的高应力。手术修复会导致光滑的界面 变成纤维（例如，进行疝气手术）或艰难的界面变得薄弱（例如， 肌腱和韧带修复）。在大肩​​袖维修的老年患者中， 例如，如果未改革所需的附件，则多达94％的手术维修失败。这些 挑战之所以出现，部分是因为赋予具有韧性的纤维接口的功能不是 已知。因此，我们建议开发一种全面的建模和实验方法 研究从纤维界面中从坚硬到弱的过渡的因素。我们的先前 工作激发了以下假设：疾病是纤维固定的关键韧性特征。我们 最初将集中在肌腱附着在骨骼上的例子上，其中显微镜障碍是基础的 有序的宏观尺度，两个时间之间的分级过渡，作为研究 整个身体的粘合剂的一般问题。我们预测疾病会增强能量 通过在大量组织上分配故障过程和能量抽象来抽象。我们 提出这是一种基本机制 有效地。我们将通过两个目的测试这些想法：（1）确定并建模 纤维固定后体内。我们将建模并通过实验验证疾病的方式 长度尺度会使肌腱对骨头的固定紧绷。层次分子动力学到 - 通过机器学习丰富的连续模型将在具有纳米级的系统中得到验证 在纤维附着的组织样品中控制矿物分布和离体。 （2）识别和 模拟使用鼠旋转器在体内因病理环境而导致的纤维固定韧性的损失 袖口肌腱病模型。在这两个目标中，都将执行纳米 - 通过毫米尺度的表征 定义驱动机械行为的机制。我们将测试病理学的假设 在多个长度尺度下诱导的变化将预测故障模式的变化。这些模型和 实验将测试全球假设，即跨层次结构的能量抽象是一个基本的假设 纤维界面可抵抗损伤水平载荷的强化机制。总的来说，我们 相信这些新的纤维依恋模型将使您能够了解秩序 纤维附着的复杂性会导致组织的有效附着。