Mechanical Consequences of Focal Articular Defects

局灶性关节缺损的机械后果

• 批准号: 8002887
• 负责人: Elise F Morgan
• 金额: $ 5.99万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8002887
• 关键词: Area; Biological; Biomechanics; Cartilage; Cell Nucleus; Chondrocytes; Competence; Defect; Elements; Environment; Fellowship; Foundations; Goals; Healed; Image; Injury; Investigation; Joints; Knee; Lead; Lesion; Liquid substance; Measures; Mechanics; Methods; Modeling; Motion; Movement; Osteoarthrosis Deformans; Physiological; Research; Research Training; Site; Slice; Slide; Specimen; Staining method; Stains; Stress; Thick; Tissues; Validation; Work; articular cartilage; cartilage repair; digital; healing; joint function; joint loading; osteochondral tissue; pressure; public health relevance; repaired; research study; skeletal

DESCRIPTION (provided by applicant): Focal articular defects are one of the most common types of articular lesions and are associated with progressive degeneration of articular cartilage in both osteoarthritic and asymptomatic knees. Prior investigations on the mechanics of focal articular defects and on cartilage mechanobiology suggest that the presence of a focal defect causes mechanical overload of the adjacent and opposing articular cartilage, and that this overload has direct consequences for the viability, mechanical competence, and mechano- responsiveness of the adjacent and opposing cartilage. Study of the mechanical environment of focal defects may therefore elucidate the biological and biomechanical mechanisms by which these defects can lead to larger scale cartilage loss and compromised joint function. However, little quantitative information is available on the intra-tissue strains, stresses, pressures, and fluid velocities in the vicinity of articular defects. This fellowship application proposes a set of initial studies that will characterize the mechanical environment of focal articular defects. These studies are the central component of the research training plan that will broaden the PI's background in the mechanobiology of skeletal healing and facilitate the PI's transition into the research area of articular cartilage defect repair. The hypothesis of the proposed work is that for physiologic joint loading, the local mechanical environment of a focal articular defect differs from that of the intact articular layer; moreover, the mechanical environment of the defect can be controlled through defined alterations in the applied joint motions. Two specific aims are proposed. Aim #1 will apply compression, sliding, and rolling movements to opposing osteochondral slices both before and after creation of a full-thickness, focal defect. The strains induced in the tissue surrounding and opposing the defect site will be measured via digital correlation of images in which the chondrocyte nuclei have been fluorescently stained. Aim #2 will estimate, using specimen-specific finite element (FE) models, the intra-tissue pressures, stresses, and fluid velocities that occur in the cartilage during the experiments in Aim #1. Validation of the FE results will be performed by comparing the FE-computed strain distributions with those measured in Aim #1. The methods and results from these studies will lay the foundation for subsequent biomechanical investigations that seek to define relationships between mechanical factors and further progression of defects, and for subsequent mechanobiological investigations aimed at manipulating the local mechanical environment in order to enhance healing. Taken together, the findings from this work will constitute an important initial milestone for an integrated approach to the biomechanics and mechanobiology of cartilage defects that should lead the way to new treatment approaches in articular cartilage repair. PUBLIC HEALTH RELEVANCE: Injuries to articular cartilage are common and are associated with progressive cartilage degeneration and loss of joint function. Although results of prior studies have suggested that the presence of a defect in articular cartilage leads to accelerated cartilage destruction through mechanical overload of the surrounding tissue, little is known about the mechanical environment of these defects. The proposed research will quantify relationships between this mechanical environment and joint loads/motions, with the long-term goal of developing new treatment approaches in articular cartilage repair.

描述（由申请人提供）：关节关节缺陷是关节病变的最常见类型之一，与骨关节炎和无症状膝盖的关节软骨进行了渐进性。先前对焦距关节缺陷和软骨机械生物学的力学的研究表明，局灶性缺陷的存在会导致相邻和相反的关节软骨的机械过载，并且这种过载具有直接的后果，对邻近和相反的Cartilage的机械能力和机械能力以及机械能力以及机械能力。因此，研究局灶性缺陷的机械环境可能会阐明这些缺陷可以导致更大规模软骨损失和关节功能损害的生物学和生物力学机制。但是，关于关节缺陷附近的组织内菌株，应力，压力和流体速度，几乎没有定量信息。该奖学金应用提出了一组初步研究，该研究将表征局灶性关节缺陷的机械环境。这些研究是研究培训计划的核心组成部分，该计划将扩大骨骼愈合机械生物学的背景，并促进PI向关节软骨缺陷修复的研究领域的过渡。拟议工作的假设是，对于生理关节载荷，局灶性关节缺陷的局部机械环境与完整的关节层不同。此外，可以通过施加的关节运动的定义改变来控制缺陷的机械环境。提出了两个具体目标。 AIM＃1将在创建全厚度，焦点缺陷之前和之后，将压缩，滑动和滚动运动应用于相对的骨软骨切片。将通过数字相关性测量图像的数字相关性，其中软骨细胞核已被荧光染色。 AIM＃2将使用标本特异性有限元（Fe）模型，在AIM＃1中实验中软骨中发生的组织内压力，应力和流体速度进行估计。 FE结果的验证将通过将FE计算的应变分布与AIM＃1中测量的分布进行比较来进行。这些研究的方法和结果将为随后的生物力学研究奠定基础，该研究旨在定义机械因素和进一步缺陷之间的关系，以及随后的机械生物学研究，旨在操纵当地机械环境以增强愈合。综上所述，这项工作的发现将是针对软骨缺陷的生物力学和机械生物学方法的重要初始里程碑，该方法应该导致关节软骨修复的新治疗方法。 公共卫生相关性：关节软骨的伤害很常见，并且与进行性软骨变性和关节功能的丧失有关。尽管先前的研究结果表明，关节软骨缺陷的存在导致通过周围组织的机械过载来加速软骨破坏，但对这些缺陷的机械环境知之甚少。拟议的研究将量化这种机械环境与关节载荷/运动之间的关系，其长期目标是开发关节软骨修复中的新治疗方法。