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）：局灶性关节缺损是最常见的关节病变类型之一，与骨关节炎和无症状膝关节的关节软骨进行性变性相关。先前对局灶性关节缺损的力学和软骨机械生物学的研究表明，局灶性缺损的存在导致相邻和对侧关节软骨的机械过载，并且这种过载对相邻和对侧软骨的活力、机械能力和机械响应性具有直接后果。因此，研究局灶性缺损的力学环境可能阐明这些缺损导致更大规模软骨损失和关节功能受损的生物学和生物力学机制。然而，在关节缺损附近的组织内应变、应力、压力和流体速度的定量信息很少。这项奖学金申请提出了一套初步的研究，将表征局部关节缺损的力学环境。这些研究是研究培训计划的核心组成部分，将拓宽PI在骨骼愈合机械生物学方面的背景，并促进PI过渡到关节软骨缺损修复的研究领域。所提出的工作的假设是，对于生理关节负荷，局部关节缺损的局部力学环境与完整关节层的局部力学环境不同;此外，缺损的力学环境可以通过应用关节运动中定义的改变来控制。提出了两个具体目标。目标#1将在创建全层局灶性缺损之前和之后对相对骨软骨切片施加压缩、滑动和滚动运动。将通过图像的数字相关性测量在缺损部位周围和对面的组织中诱导的应变，其中软骨细胞核已被荧光染色。目标#2将使用软骨特异性有限元（FE）模型估计目标#1实验期间软骨中发生的组织内压力、应力和流体速度。将通过比较FE计算的应变分布与目标#1中测量的应变分布，对FE结果进行确认。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，这些研究旨在确定机械因素与缺损进一步进展之间的关系，并为随后的机械生物学研究奠定基础，这些研究旨在操纵局部机械环境以增强愈合。总之，这项工作的发现将构成软骨缺损的生物力学和机械生物学综合方法的一个重要的初始里程碑，这将为关节软骨修复的新治疗方法开辟道路。 公共卫生相关性：关节软骨损伤是常见的，并且与进行性软骨退化和关节功能丧失有关。虽然先前的研究结果表明，关节软骨中存在的缺陷会通过周围组织的机械过载导致加速软骨破坏，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力学环境与关节载荷/运动之间的关系，长期目标是开发关节软骨修复的新治疗方法。