Aging Osteoarthritis Effect on Structure-Function of Human Meniscal Attachments

项目概要/摘要： 半月板是纤维软骨结构，有助于负荷分布和关节润滑。他们的 功能性部分依赖于将RPCCI连接到底层的唯一分级接口 骨头这些界面的微观结构证明了它们的功效，因为它们减轻了应力 在每天的活动过程中，这些界面的缓慢退化 时间可能会促进骨关节炎的传播。假设随着年龄的增长 在附着位点上的材料性质差异增加，破坏了 压缩以减弱载荷，导致过度的挤压和关节磨损增加。 目前的文献未能确定如何生物化学和形态结构的胰岛 附件从纤维软骨过渡到下面的软骨下骨。其目的是 研究计划将弥合在机械环境的理解，这些差距 界面必须持久，以及这如何导致它们的结构发展。这项工作直接 可转化为开发病变组织的工程替代品，因为目前的策略仍然是 尽管它们的有效性依赖于仿生固定的需要， 战略 本研究的第一个目的是确定口腔附着体内部的力学环境 as a function函数of age年龄.在生理和生理过程中， 健康、ACL横断/部分切除和老年骨关节炎的病理负荷 膝盖将被测量。膝关节将动态压缩至体重的21/2倍， 根据生理负荷/屈曲角度数据，同时测量 附件原位，使用新型光纤压力微传感器。第二个目标是量化 作为年龄函数的过渡区的材料特性和矿化度，包括 健康和骨关节炎性关节附件。半月板附件将从 动态测试膝关节。将确定过渡区的材料特性， 使用纳米压痕仪的人体骨附着物。将使用以下方法确定钙化 定量背散射电子显微术这些数据将进行统计学比较，以阐明 区域和解剖位置之间的差异作为年龄的函数。 骨关节炎的症状可以发展为年轻的40岁，然而，其患病率增加到 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关节炎的主要原因。 工作残疾和生活质量下降。老年人减少到不能走动的状态， 危及生命的疾病，如心脏病和糖尿病的风险更大。这 研究将有可能彻底改变我们的老年人护理，并奠定基础， 预防技术，为潜在的风险患者，年轻人和老年人，以及组织工程 替代那些已经患有骨关节炎的人。 该项目致力于描述一个复杂的生物结构，确定一个根本原因， 与年龄有关的疾病，并在同龄人中传播研究结果。为了实现这些目标，培训是 跨科学，技术和通信研究领域所需的。解释一下， 培训计划需要培养熟练掌握尖端生物研究工具，包括 压力微传感器，扫描电子显微镜和纳米压痕，通过实质性的 与领先的研究科学家合作。能力、相关性和进展将定期 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机会，以加强国家的艺术，但也有助于引导 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.