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，并且与骨关节炎和无症状膝盖的关节软骨进行性退化相关。先前对局灶性关节缺陷的力学和软骨力学生物学的研究表明，局灶性缺陷的存在会导致相邻和相对关节软骨的机械过载，并且这种过载对相邻和相对软骨的生存能力、机械能力和机械响应性有直接影响。因此，对局灶性缺陷的机械环境的研究可能会阐明这些缺陷导致更大规模的软骨损失和关节功能受损的生物学和生物力学机制。然而，关于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。该奖学金申请提出了一系列初步研究，这些研究将描述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，将拓宽 PI 在骨骼愈合力学生物学方面的背景，并促进 PI 过渡到关节软骨缺损修复研究领域。这项工作的假设是，对于生理关节负荷，局灶性关节缺损的局部机械环境与完整关节层的局部机械环境不同；此外，可以通过所施加的关节运动的限定改变来控制缺陷的机械环境。提出了两个具体目标。目标#1 将在形成全层局灶性缺损之前和之后对相对的骨软骨切片施加压缩、滑动和滚动运动。将通过软骨细胞核已被荧光染色的图像的数字关联来测量缺损部位周围和相对的组织中引起的应变。目标#2 将使用样本特定的有限元 (FE) 模型来估计目标#1 实验期间软骨中出现的组织内压力、应力和流体速度。有限元结果的验证将通过将有限元计算的应变分布与目标#1 中测量的应变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，这些研究旨在确定机械因素与缺陷进一步进展之间的关系，以及旨在操纵局部机械环境以促进愈合的后续机械生物学研究。总而言之，这项工作的结果将构成软骨缺陷生物力学和力学生物学综合方法的一个重要的初步里程碑，这应该为关节软骨修复的新治疗方法指明道路。 公众健康相关性：关节软骨损伤很常见，并且与进行性软骨退化和关节功能丧失有关。尽管先前的研究结果表明关节软骨缺陷的存在会通过周围组织的机械超负荷导致加速软骨破坏，但人们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负荷/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。