Anisotropic and Nonlinear Structure-Function of Normal and Degenerate Tendon

描述（由申请人提供）：由于退变和/或损伤引起的肩袖损伤是一种常见的导致严重疼痛和残疾的原因，在工作场所，娱乐，运动和老龄化环境中，影响年轻人和老年人。与大多数肌腱不同，冈上肌腱必须定期承受复杂的载荷环境，包括多轴拉伸、压缩和剪切，这使得研究冈上肌腱问题变得困难。复杂的载荷是由于其解剖结构，由周围软组织、喙峰弓、斜插入角度和非均匀纤维取向产生的非单轴力。为了理解、预测、预防和治疗冈上肌退变和损伤，以及设计组织工程替代结构，对冈上肌在正常和改变条件下的机械能力有一个完整的了解是至关重要的。因此，本研究计划的目的是严格评估正常和退化冈上肌腱的各向异性和非线性结构-功能关系。具体而言，我们提出了以下两个目标：目标1：量化正常和退化的人冈上肌腱在多种载荷模式下的非线性和各向异性力学行为和胶原纤维重定向，包括：纤维定向和横向的单轴张力，双轴张力和平面剪切。量化机械测试样品相邻位置的生化成分和组织学等级。目标2：开发和应用非线性各向异性本构模型来预测肌腱结构功能关系。明确纳入纤维分布和纤维在负荷下的重新定向，以及纤维拉伸、纤维外基质和纤维-基质相互作用对肌腱功能的贡献。利用Aim 1的双轴和剪切实验数据确定模型参数，并通过预测单轴拉伸数据验证模型。将模型参数与组成测量相关联，完成结构-组成-功能的量化，并对这些关系与区域和退化的假设进行检验。了解这些关系将为理解驱动正常组织适应和衰老的基本机制、疾病过程和潜在治疗以及组织工程替代结构的设计提供重要信息。

DESCRIPTION (provided by applicant): Rotator cuff damage due to degeneration and/or injury is a common cause of significant pain and disability affecting the young and old alike in workplace, recreational, athletic, and aging environments. Different from most tendons, the supraspinatus tendon must regularly withstand a complex loading environment including multi-axial tension, compression, and shear, which makes study of this problem difficult. The complex loading is due to its anatomical structure, with non-uniaxial forces generated by the surrounding soft tissues, the coracoacromial arch, oblique insertion angles, and non-uniform fiber orientations. In order to understand, predict, prevent, and treat supraspinatus degeneration and injury, as well as to design tissue engineered replacement structures, it is critical to develop a complete understanding of the mechanical capability of this tissue in normal and altered conditions. Therefore, the objective of this research program is to rigorously evaluate anisotropic and nonlinear structure-function relationships in normal and degenerate supraspinatus tendons. Specifically, we propose the following 2 aims: Aim 1: Quantify nonlinear and anisotropic mechanical behavior and collagen fiber re-orientation of normal and degenerated human supraspinatus tendon under multiple loading modalities including: uniaxial tension in the fiber-aligned and transverse directions, biaxial tension, and planar shear. Quantify biochemical composition and histological grade at adjacent locations to the mechanical test samples. Aim 2: Develop and apply a nonlinear anisotropic constitutive model to predict tendon structure-function relationships. Explicitly incorporate fiber distribution and fiber re-orientation under load and the contribution of fiber stretch, extrafibrillar matrix, and fiber-matrix interactions to tendon function. Determine the model parameters using the biaxial and shear experimental data from Aim 1 and validate the model by predicting the uniaxial tension data. Correlate model parameters with composition measurements to complete the structure-composition-function quantification and test hypotheses for these relationships with region and degeneration. Knowledge of these relationships will provide important information towards understanding the fundamental mechanisms driving normal tissue adaptation and aging, disease processes and potential treatments, and the design of tissue engineered replacement structures. PUBLIC HEALTH RELEVANCE: Rotator cuff damage due to degeneration and/or injury is a common cause of significant pain and disability affecting the young and old alike in workplace, recreational, athletic, and aging environments. Treatment strategies aim to restore mechanical function; however, tendon anisotropic and nonlinear mechanical behaviors are not well established. Therefore, the objective of this research program is to determine quantitative anisotropic and nonlinear structure-function relationships in normal and degenerate supraspinatus tendons.