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。膝关节韧带损伤是最常见的骨科损伤之一。它们通常发生在膝盖被迫超出其正常活动范围时，例如在跌倒时。当膝盖受到冲击时，比如在车祸或足球铲球时，也会发生这种情况。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。虽然许多生物力学研究人员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，但很少有人知道它们对导致部分和完全失效的机械刺激的反应。特别是，需要研究阐明与部分撕裂和完全撕裂相关的微观结构变化。第一次，本构关系的作用，解释微观结构在损伤演变过程中的韧带将得到发展。这些模型将通过将提供胶原交联和胶原分子损伤信息的分子模型与结构连续体模型相结合而得到。结构模型将考虑到韧带组织的组成，它们的几何排列和它们之间的相互作用。他们将描述典型的各向异性、非线性和韧带组织所表现出的非弹性。在理论研究的同时，将进行力学和显微实验来量化胶原蛋白分子间交联对韧带失效的影响。为此，从两组动物身上采集的膝关节韧带，一组饲喂正常饮食，另一组饲喂促炎性饮食，将沿着其生理方向遭受不同的亚失效拉伸。将检查韧带的微观结构损伤，并评估胶原蛋白的分子碎片，以确定韧带是如何在分子水平上发生失效的。反过来，这些信息将与基于力学数据开发的结构模型相关联。总之，这三种方法将有助于更全面地了解韧带成分的结构/功能关系。知识价值。成功完成拟议的项目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将结合他们在连续介质力学（R. De Vita），分子模型（J. W. Freeman），实验力学（J. G. Barrett， R. De Vita和J. W. Freeman）和分子生物学（J. G. Barrett）方面的专业知识，制定新的模型，结合力学和微观实验将阐明韧带损伤发展和材料组成之间的关系。该研究项目将通过为开发韧带替代品提供机械和结构特性的知识，对替代移植物和生物支架的工程材料领域产生重大影响。结果还可以指导设计支架或拉伸程序，以限制韧带劳损，防止在紧张活动中损伤。由于韧带具有非常良好的组织结构和相对简单的组成，因此研究结果将有助于理解更复杂的生物软组织（例如皮肤和动脉）的失效机制。更广泛的影响。本科生和研究生将参与研究项目的理论、数值和实验部分。pi将与生物信息学和生物工程暑期学院项目和大学绑定项目合作，以吸引和留住未被充分代表的科学和工程群体。研究成果将纳入本科、研究生和专业课程的现行课程。研究结果将在国内和国际会议上发表，并在同行评议的期刊上发表。

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.