Multiscale models of fibrous interface mechanics

项目摘要 来自母公司的资助：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（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-肠系膜界面之间的界面。 血管和软脑膜这些界面需要韧性以抵抗与表面张力相关的高应力。 材料不匹配。手术修复可导致光滑界面变成纤维状（例如，继发疝 外科手术）或坚韧的界面变得脆弱（例如，在肌腱-和韧带-骨修复之后）。老年 例如，患有大型肩袖修复术的患者，其中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 韧性未知。因此，我们建议开发一个全面的建模和实验 研究纤维界面由坚韧向弱转变的因素的方法。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。我们将重点 最初以肌腱附着在骨骼上为例，其中微观无序是有序的基础， 宏观尺度，两种组织之间的梯度过渡，作为研究的一般问题的基础， 粘附在整个身体。我们预测，无序通过分布失效来增强能量吸收 在更大体积的组织上的过程和能量吸收。我们建议将此作为一种基本机制 通过其身体中的纤维界面有效地传递负荷。我们将通过两个目标来检验这些想法： (1)识别和模拟纤维附着增韧离体的机制。我们将模型和 通过实验验证长度尺度上的紊乱如何使肌腱-骨附着变硬。分层 通过机器学习丰富的分子动力学到连续统模型将在体外系统中进行验证， 在纤维附着的组织样品中，对矿物质分布进行纳米级控制。(2)识别 并使用小鼠肩袖在体内模拟由于病理环境引起的纤维附着韧性的损失 肌腱病变模型。在这两个目标中，将进行纳米到毫米尺度的表征，以确定 驱动机械行为的机制。我们将检验以下假设： 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这一假设 跨层次的能量吸收是一种基本的增韧机制， 抗损伤水平载荷。综上所述，我们相信这些新的纤维附着模型将使 理解纤维附着的顺序和复杂性如何导致组织的有效附着。

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.