Multiscale models of fibrous interface mechanics

项目总结 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载荷方面非常有效，例如， 在结缔组织-骨界面处，腹膜-肠系膜界面，界面 在血管系统层和软脑膜层之间。这些界面需要韧性才能抵抗 与材料不匹配相关的高应力。手术修复可以使界面光滑 变得纤维化(例如，在疝气手术之后)或变得坚硬的界面变弱(例如， 在肌腱和韧带到骨骼的修复之后)。在接受大型肩袖修复的老年患者中， 例如，如果所需的附着体没有改造，高达94%的外科修复失败。这些 挑战之所以出现，部分是因为赋予纤维界面韧性的特征不是 为人所知。因此，我们建议开发一种全面的建模和实验方法 研究纤维界面中从坚韧到脆弱转变的潜在因素。我们以前的 这项工作支持了这样一种假设，即无序是纤维连接的一个关键增韧特征。我们 我将首先关注肌腱附着在骨骼上的例子，在这种例子中，微尺度的紊乱是基础 这两种组织之间的有序的宏观尺度的、分级的过渡，作为研究 全身粘连的普遍问题。我们预测无序会增强能量 通过将失效过程和能量吸收分散到更大体积的组织来进行吸收。我们 建议将其作为身体中纤维界面传递载荷的基本机制 有效地。我们将通过两个目标来测试这些想法：(1)识别和模拟 纤维附着在体外增韧。我们将建立模型并通过实验验证无序 横跨长度的鳞片使肌腱与骨骼的连接变得更坚韧。层次化分子动力学 由机器学习丰富的连续体模型将在体外进行验证，在具有纳米级的系统中 控制纤维附着体组织样本中的矿物质分布和体外。(2)识别和 用小鼠旋转器模拟体内病理环境下纤维附着韧性的丧失 袖带肌腱病模型。在这两个目标中，都将进行纳米级到毫米级的表征 定义驱动机械行为的机制。我们将测试病理学的假说- 在多个长度尺度上的诱导变化将预测故障模式的变化。这些型号和 实验将检验全球假设，即跨层次的能量吸收是 纤维界面抵抗损伤水平载荷的增韧机制。总而言之，我们 相信这些纤维附着的新模型将使我们能够理解 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.