Biotribology of Diarthrodial Joints

描述(申请人提供)：关节软骨的主要功能是作为腹泻关节的承重材料。作为我们最近研究的一部分，我们从理论和实验中证明了软骨即使在边界摩擦的情况下也能提供有效的润滑，主要是因为它的间隙水在载荷下可能会产生相当大的压力。在这一应用中，我们建议通过解决与腹泻关节中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对功能有害的值，是什么使其在生理负载条件下保持足够低的原位？B)在考虑了间质液体负荷支持的作用后，滑液中的边界润滑剂有多有效？C)在对关节载荷的初始响应中，是否存在润滑剂暂时滞留在关节表面之间的功能显著的混合润滑状态？如果是，这种混合状态的持续时间是否取决于润滑剂的类型？虽然从临床和商业的角度来看，从滑液及其成分(例如，关节内注射透明质酸和其他“润滑剂”)引起的一种现象来考虑关节润滑可能是有吸引力的，但它们对关节软骨低摩擦特性的相对贡献尚不清楚。我们提出了一个独创的理论框架，并利用过去两个授权期开发的新实验技术进行了验证，这些技术清楚地描述了即使在没有滑液的情况下，关节软骨也能够表现出极低的摩擦系数，现在我们提出了一些研究，以确定滑液中的边界润滑剂对腹泻性关节润滑机制的功能有效性的贡献。我们的建议是及时的，考虑到最近对滑液或关节软骨表层的蛋白质的兴趣的复苏，这可能有助于摩擦学反应。为了验证我们的假设，该提议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.