Micro-Mechanical Characterization of Damage in Ligaments

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。“0932024 De Vita膝盖韧带扭伤是最常见的骨科损伤之一。它们通常发生在膝关节被迫超出其正常运动范围时，例如跌倒。它们也发生在膝盖受到冲击时，例如在车祸或足球铲球中。这些损伤可能包括轻微的过度拉伸、部分撕裂或韧带完全断裂。虽然生物力学领域的许多研究人员都专注于量化韧带的材料特性，如切线模量、拉伸强度和极限应变，但对韧带对导致部分和完全失效的机械刺激的反应知之甚少。特别是，需要研究来阐明与部分和完全撕裂相关的微观结构变化。 第一次，本构关系，解释的作用，微观结构的损伤演化过程中的韧带将开发。这些模型将通过整合分子模型来获得，这些分子模型提供了关于胶原交联和胶原分子损伤的信息，并具有结构连续模型。结构模型将通过考虑韧带组织的组分、它们的几何排列和它们的相互作用来制定。他们将描述韧带组织表现出的典型的各向异性、非线性和非弹性。在理论研究的同时，还将进行力学和微观实验，以量化胶原分子间交联对韧带失效的影响。为此，将从两组动物（一组用正常饮食喂养，另一组用乳酸菌饮食喂养）收获的膝关节韧带沿其生理方向进行沿着不同的亚失效拉伸。 将检查韧带的微观结构损伤，并评估胶原蛋白的分子碎片，以确定韧带如何在分子水平上发生失效。这些信息将反过来与基于力学数据开发的结构模型相关联。总之，这三种方法将最终在一个更完整的了解韧带的组成部分的结构/功能关系。智力优点。拟议项目的成功完成需要生物系统的理论和实验力学以及分子生物学的综合知识。PI将联合收割机他们在连续介质力学（R。De Vita）、分子建模（J. W. Freeman），实验力学（J.G.巴雷特河De Vita和J. W. Freeman）和分子生物学（J. G. Barrett）提出了新的模型，结合力学和微观实验，将阐明损伤发展与韧带材料组成之间的关系。该研究计划将通过提供机械和结构特性的知识，以开发韧带替代品，在替代移植物和生物支架的工程材料领域产生重大影响。研究结果还可以指导支架或拉伸程序的设计，以限制韧带应变，从而防止在压力活动中造成损伤。由于韧带具有非常良好的组织结构和相对简单的组成，研究结果将有助于了解更复杂的生物软组织（例如皮肤和动脉）的失效机制。本科生和研究生将从事研究项目的理论，数值和实验部分。PI将与生物信息学和生物工程暑期研究所计划和学院绑定计划合作，以吸引和保留代表性不足的群体到科学和工程。研究结果将被纳入目前在本科生，研究生和专业课程提供的课程。研究结果将在国家和国际会议上发表，并发表在同行评审的期刊上。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5)."0932024De VitaSprains of the knee ligaments are among the most common orthopedic injuries. They usually occur when the knee is forced beyond its normal range of motion, such as in a fall. They also happen when the knee experiences an impact, such as in a car accident or during a football tackle. These injuries can consist of a slight over-stretch, a partial tear, or a complete disruption of the ligaments. While many investigators in biomechanics have focused on quantifying the material properties of ligaments, such as tangent modulus, tensile strength, and ultimate strain, little is know of their response to mechanical stimuli that lead to partial and complete failure. In particular, studies are needed to clarify the micro-structural changes associated with partial and complete tears. For the first time, constitutive relationships that explain the role of microstructure in the damage evolution process of ligaments will be developed. These models will be derived by integrating molecular models that provide information about collagen cross-linking and collagen molecular damage with structural continuum models. The structural models will be formulated by taking into account the components of the ligamentous tissues, their geometrical arrangement, and their interactions. They will describe the typical anisotropy, nonlinearity, and inelasticity exhibited by ligamentous tissue. Together with the theoretical study, mechanical and microscopic experiments will be performed to quantify the effect of collagen intermolecular cross-linking on the failure of ligaments. Toward this end, knee ligaments harvested from two groups of animals, one fed with a normal diet and another fed with a lathyritic diet, will be subjected to different sub-failure stretches along their physiological direction. Ligaments will be examined for microscopic structural damage, and molecular fragmentation of collagen _brils will be assessed to determine how ligament failure occurs on a molecular level. This information will, in turn, be correlated to the structural models developed based upon the mechanical data. Together, these three approaches will culminate in a more complete understanding of the structure/function relationship of the components of ligament.Intellectual Merit. The successful completion of the proposed project requires a combined knowledge of theoretical and experimental mechanics of biological systems as well as molecular biology. The PIs will combine their expertise in continuum mechanics (R. De Vita), molecular modeling (J. W. Freeman), experimental mechanics (J. G. Barrett, R. De Vita and J. W. Freeman) and molecular biology (J. G. Barrett) to formulate novel models that together with mechanical and microscopic experiments will elucidate the relationship between damage development and material composition of ligaments. This research program will have a signifcant impact in the area of engineering materials for replacement grafts and biological scaffolds by offering a knowledge of mechanical and structural properties to target in developing replacements for ligaments. The results can also guide the design of braces or stretching routines to limit ligament strain so as prevent damage during stressful activities. Because ligaments possess a very well organized structure and a relatively simple composition, the research findings will contribute to understanding the failure mechanism of more complex biological soft tissues such as, for example, skin and arteries.Broader Impacts. Undergraduate and graduate students will be engaged in the theoretical, numerical, and experimental components of the research project. The PIs will work with the Bioin-formatics and Bioengineering Summer Institute program and the College Bound program to attract and retain underrepresented groups to science and engineering. Research findings will be incorporated into current courses that are offered in the undergraduate, graduate and professional curricula. The results of the research will be presented at national and international conferences and published in peer-reviewed journals.