Micro-Mechanical Characterization of Damage in Ligaments

该奖项由2009年《美国复苏和再投资法案》(公法111-5)资助。它们通常发生在膝盖被强迫超出其正常运动范围时，例如在摔倒时。当膝盖受到撞击时，如车祸或足球铲球时，也会发生这种情况。这些损伤可能包括轻微的过度伸展、部分撕裂或韧带完全断裂。虽然许多生物力学研究人员都专注于量化韧带的材料特性，如切线弹性模量、拉伸强度和极限应变，但对导致部分和完全断裂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结构变化。首次建立了解释微结构在韧带损伤演化过程中的作用的本构关系。这些模型将通过将提供关于胶原交联和胶原分子损伤的信息的分子模型与结构连续体模型相结合而得到。结构模型将通过考虑韧带组织的成分、它们的几何排列以及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、非线性和无弹性。结合理论研究，将进行力学和显微实验，以量化胶原分子间交联在韧带断裂中的作用。为此，从两组动物中获取的膝关节韧带，一组喂以正常饮食，另一组喂以低蛋白饮食，将沿着其生理方向受到不同的亚失效伸展。将检查韧带的微观结构损伤，并将评估胶原蛋白的分子断裂，以确定韧带断裂是如何在分子水平上发生的。这些信息将依次与基于力学数据开发的结构模型相关联。综合起来，这三种方法最终将导致对韧带组件的结构/功能关系的更全面的了解。成功完成拟议的项目需要结合生物系统和分子生物学的理论和实验力学知识。PI将结合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.Barrett、R.de Vita和J.W.Freeman)和分子生物学(J.G.Barrett)的专业知识来建立新的模型，这些模型与力学和显微实验一起将阐明韧带损伤发展和材料组成之间的关系。这项研究计划将在替代移植物和生物支架的工程材料领域产生重大影响，为开发韧带替代物的目标提供力学和结构特性方面的知识。这些结果也可以指导设计支架或伸展程序，以限制韧带拉伤，以防止在应激性活动中的损伤。由于韧带具有组织良好的结构和相对简单的成分，研究成果将有助于理解更复杂的生物软组织的破坏机制，例如皮肤和动脉。本科生和研究生将参与研究项目的理论、数值和实验部分。PIS将与生物信息学和生物工程暑期学院计划和大学边界计划合作，以吸引和留住未被充分代表的群体进入科学和工程领域。研究成果将被纳入本科生、研究生和专业课程提供的现有课程。研究结果将在国内和国际会议上公布，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.