Biotribology of Diarthrodial Joints

描述（由申请人提供）：关节软骨的主要功能是作为腹泻关节的承载材料。作为我们最近研究的一部分，我们已经从理论和实验中证明，即使在边界摩擦下，软骨也可以提供有效的润滑，主要是因为其间隙水在负载下可能会产生相当大的压力。在本申请中，我们建议通过解决与双关节润滑机制的功能有效性相关的具体问题来跟进这些发现：a)由于在实验室测试条件下观察到摩擦系数随着时间的推移而增加到功能有害的值，是什么使得它在原位的生理负载条件下保持足够低？b)考虑到间质液负载支持的作用后，滑液中的边界润滑剂的效果如何？c)在关节加载的初始响应中，是否存在一个功能显著的混合润滑机制，在此期间，润滑剂暂时被困在关节表面之间，如果有，这种混合机制的持续时间是否取决于润滑剂的类型？虽然从临床和商业角度来看，考虑关节润滑是一种由滑液及其成分（例如，关节内注射透明质酸和其他“润滑剂”）引起的现象可能很有吸引力，但它们对关节软骨低摩擦特性的相对贡献尚未得到很好的理解。在最初的理论框架下，使用过去两个授权期开发的新实验技术进行验证，清楚地描述了即使在没有滑液的情况下，关节软骨如何能够表现出极低的摩擦系数，我们现在提出研究，以确定滑液中的边界润滑剂对滑膜关节润滑机制的功能有效性的贡献。我们的建议是及时的，因为最近对滑膜液或关节软骨表面区蛋白质的兴趣重新抬头，这可能有助于摩擦学反应。为了验证我们的假设，该提案结合了原子力显微镜（AFM），全内反射荧光（TIRF）显微镜和扫描共聚焦显微镜（SCM）技术的一些新应用。

DESCRIPTION (provided by applicant): The primary function of articular cartilage is to serve as a bearing material for diarthrodial joints. As part of our recent studies, we have demonstrated from theory and experiments that cartilage can provide efficient lubrication even under boundary friction, primarily because its interstitial water may pressurize considerably under loading. In this application, we propose to follow-up on these findings by addressing specific questions related to the functional effectiveness of the lubrication mechanism in diarthrodial joints: a) Since the friction coefficient is observed to increase over time to functionally detrimental values under laboratory testing conditions, what makes it stay sufficiently low under physiological loading conditions in situ? b) How effective are the boundary lubricants in synovial fluid, after accounting for the role of interstitial fluid load support? c) Is there a functionally significant mixed lubrication regime in the initial response to joint loading during which lubricant is temporarily trapped between articular surfaces, and if so, does the duration of this mixed regime depend on the type of lubricant? While it may be attractive from the clinical and commercial perspective to consider joint lubrication in terms of a phenomenon arising from synovial fluid and its constituents (e.g., intra-articular injection of hyaluronan and other "lubricants"), their relative contribution to the low frictional properties of articular cartilage are not well understood. With an original theoretical framework, validated using novel experimental techniques developed over the past two granting periods that clearly describe how articular cartilage is able to exhibit extremely low friction coefficients even in the absence of synovial fluid, we now propose studies to determine the contribution of boundary lubricants in synovial fluid to the functional effectiveness of the lubrication mechanism in diarthrodial joints. Our proposal is timely in light of the recent resurgence of interest in proteins in synovial fluid or in the superficial zone of articular cartilage that may assist in the tribological response. To investigate our hypotheses, the proposal incorporates some novel applications of Atomic Force Microscopy (AFM), Total Internal Reflectance Fluorescence (TIRF) microscopy, and Scanning Confocal Microscopy (SCM) techniques.