Multiscale models of fibrous interface mechanics

项目摘要 组织之间的界面要么传递载荷（需要韧性），要么提供光滑的表面 （需要低摩擦）。纤维界面在组织之间传递负荷时非常有效，例如， 在结缔组织-骨界面（“附着点”）、腹膜-肠系膜界面、界面 在血管系统和软脑膜之间。这些界面需要韧性来抵抗 与材料不匹配相关的高应力。手术修复可使界面光滑 变成纤维状，（例如，在疝手术之后）或坚韧的界面变得脆弱（例如， 在肌腱-和韧带-骨修复之后）。在大型肩袖修复的老年患者中， 例如，如果所需的附件没有重新形成，高达94%的手术修复失败。这些 挑战的出现部分是因为赋予纤维界面韧性的特征并不 知道的因此，我们建议开发一个全面的建模和实验方法， 研究纤维界面由坚韧向弱转变的因素。我们以前的 功激发了无序是纤维附着的关键增韧特征的假设。我们 我将首先集中在肌腱附着在骨骼上的例子上，在这个例子中，微尺度的无序是 有序的宏观尺度，两种组织之间的梯度过渡，作为研究的基础， 整个身体的普遍问题。我们预测无序会增强能量 通过将失效过程和能量吸收分布在更大体积的组织上来吸收。我们 我认为这是身体中纤维界面传递负荷的基本机制 有效地我们将通过两个目标来测试这些想法：（1）识别和建模 离体纤维附着增韧。我们将模拟和实验验证无序 在长度尺度上加强了腱-骨连接。分级分子动力学 通过机器学习丰富的连续体模型将在体外，在具有纳米尺度的系统中进行验证。 控制矿物分布，离体，在纤维附件的组织样品中。(2)识别和 使用小鼠旋转器在体内模拟由于病理环境引起的纤维附着韧性损失 袖状肌腱病模型。在这两个目标中，将进行纳米到毫米级的表征， 定义驱动机械行为的机制。我们将检验病理学- 在多个长度尺度下的诱导变化将预测失效模式的变化。这些模型和 实验将测试全球假设，即跨层次的能量吸收是一个基本的 纤维界面抵抗损伤水平载荷的增韧机制。总之，我们 我相信，这些新的纤维附着模型将使我们能够理解 并且纤维附着的复杂性导致组织的有效附着。

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.