Aging Osteoarthritis Effect on Structure-Function of Human Meniscal Attachments

项目摘要/摘要： 半月板是纤维软骨结构，有助于负荷分配和关节润滑。他们的 功能在一定程度上依赖于将半月板连接到底层的唯一分级界面 骨头。这些界面的微观结构证明了它们缓解应力的有效性 在日常活动中在关节内发展；然而，这些界面的缓慢退化 时间可能促进了骨性关节炎的传播。据推测，随着我们在那里变老 成为连接位置中增加的材料特性差异，破坏了 半月板会减弱载荷，导致半月板过度挤压，增加关节磨损。 目前的文献未能定义半月板的生化和形态结构 附着物从纤维软骨过渡到下面的软骨下骨。这样做的目的是 研究计划将弥合对机械环境的理解上的差距，这些 接口必须经久不衰，以及这是如何导致其结构发展的。这项工作是直接 在当前策略保持不变的情况下，可翻译为开发用于疾病组织的工程化替代物 固定在半月板上，尽管它们的有效性依赖于生物模拟固定的需要 策略。 本研究的第一个目的是确定半月板附着体内的机械环境。 作为年龄的函数。半月板附着体在生理和运动过程中的内流体压力 健康、前交叉韧带横断/部分半月板切除和老年骨关节炎的病理负荷 将测量膝盖的尺寸。膝关节将被动态压缩至体重的21/2倍， 与生理负荷/屈曲角度数据一致，同时测量 就地附着物，使用新型光纤压力微型传感器。第二个目标是量化 过渡带的材料特性和矿化程度随年龄变化，包括 健康的和骨关节炎的半月板附着物。半月板附着物将从 动态测试膝关节。将确定以下过渡区的材料属性 使用纳米压痕的人体半月板附着体。将使用以下方法确定钙化程度 定量背散射电子显微镜。这些数据将进行统计比较，以阐明 区域和解剖位置之间的差异是年龄的函数。 骨关节炎症状可以在40岁时出现，然而，其患病率增加到 在65岁以上的成年人中有50%。这种疾病导致的关节功能受限是导致 工作残疾和生活质量下降。减少到非活动状态的老年人是 面临着心脏病和糖尿病等威胁生命的更大风险。这 研究可能会给我们的老年人护理带来革命性的变化，并为开发 针对潜在高危患者的预防技术，无论老少，以及组织工程 为那些已经患有骨性关节炎的人提供替代品。 这个项目致力于描述一种复杂的生物结构，确定一种 与年龄相关的疾病，并在同龄人中传播研究结果。要实现这些目标，培训就是 在科学、技术和通信研究领域都需要。明确地说， 培训计划要求熟练掌握尖端生物研究工具，包括 压力微型传感器、扫描电子显微镜和纳米压痕 与领先的研究科学家合作。能力、相关性和进步将定期 将由跨越机械、生物和医学学科的不同科学受众进行评估。 这一努力不仅将提供一个支持最先进水平的机会，而且还将有助于 并加速另一种思维进入与年龄相关的研究领域。

Project Summary/Abstract: Menisci are fibrocartilagenous structures that aid in load distribution and joint lubrication. Their functionality relies in part on the uniquely graded interfaces that join the menisci to the underlying bone. The microstructure of these interfaces is a testament to their efficacy as they mitigate stresses developed in the joint during every day activity; however, slow degradation of these interfaces over time may be facilitating the propagation of osteoarthritis. It is hypothesized that as we age there becomes an increased material property disparity in the attachment sites undermining the ability of menisci to attenuate loading, leading to excessive meniscal extrusion and increased wear on the joint. Current literature fails to define how the biochemical and morphological construct of the meniscal attachments transition from fibrocartilage to the underlying subchondral bone. The aims of this research plan will bridge a gap in the understanding of the mechanical environment that these interfaces must endure and how this has led to their structural development. This work is directly translatable to developing engineered replacements for diseased tissue as current strategies remain fixated on the meniscal body, despite their effectiveness relying on the need for a bio-mimetic fixation strategy. The first aim of this study is to determine the mechanical environment within meniscal attachments as a function of age. The internal fluid pressures in meniscal attachments during physiological and pathological loading of healthy, ACL transected/partially menisectomized, and aged osteoarthritic knees will be measured. Knee joints will be dynamically compressed up to 21/2X body weight, in accordance with physiological load/flexion angle data, while measuring fluid pressures in the attachments in situ, using novel fibre-optic pressure microsensors. The second aim is to quantify the material properties and degree of mineralization at the transition zone as a function of age, including healthy and osteoarthritic meniscal attachments. Meniscal attachments will be excised from the dynamically tested knee joints. The material properties will be determined for the transition zones of human meniscal attachments using a nanoindenter. Calcification will be determined using quantitative backscattered electron microscopy. These data will be statistically compared to elucidate differences between zones and anatomical location as a function of age. Osteoarthritis symptoms can develop as young as 40 years old, however, its prevalence increases to 50% among adults over 65. Limited joint functionality as a result of this disease is a major cause of work disability and reduced quality of life. Elderly individuals reduced to non-ambulatory states are imperiled to greater risks of life threatening conditions such as heart disease and diabetes. This research will potentially revolutionize the care of our elderly and lay the groundwork to develop preventative techniques for potential at risk patients, young and old, as well as tissue engineered replacements for those already suffering with osteoarthritis. This project strives to characterize a complex biological structure, determine a root mean cause for an age-related disease, and disseminate the findings amongst peers. To accomplish these aims training is required across scientific, technical, and communication fields of study. Explicitly, the goals of the training plan entail developing proficiency with cutting edge biological research tools including pressure microsensors, scanning electron microscopy, and nanoindentation, by means of substantive collaboration with leading research scientists. Competency, relevance, and progression will regularly be evaluated by a diverse scientific audience spanning mechanical, biological, and medical disciplines. This endeavor will not only afford an opportunity to bolster the state of the art but also serve to induct and accelerate another mind into the field of age-related research.