How Cartilage Works: Unifying Interstitial Lubrication and Hydrodynamics to Explain Joint Function

软骨如何工作：统一间质润滑和流体动力学来解释关节功能

• 批准号: 1635536
• 负责人: Christopher Price
• 金额: $ 40万
• 依托单位: University of Delaware
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1635536&HistoricalAwards=false
• 关键词: How; Cartilage; Works; Unifying; Interstitial

Under physiological contact pressures, joint spaces thin as interstitial fluid is driven from articular cartilage. Because cartilage relies on interstitial fluid for its mechanical and lubrication functions, unbalanced exudation necessarily leads to increased friction, cartilage wear, and joint disease. Fortunately, cartilage and joint space actually thicken during physical activity due to the recovery of interstitial fluid in healthy joints. The only, and accepted, hypothesis for this recovery is that "dehydrated" cartilage regions passively uptake fluid when they become exposed to the bath by contact migration. However, recent in-situ studies have shown activity-induced recovery comparable to that observed in-vivo without ever exposing the contact to the bath; the phenomenon is called "tribological rehydration" because it is induced by sliding rather than migration. These preliminary results suggested that the balance between interstitial fluid loss and recovery in active joints is regulated by the interaction between interstitial (within cartilage) and hydrodynamic (between cartilage) pressure fields. The present study tests this hypothesis using explant tribology experiments with in-situ confocal imaging to elucidate the mechanisms involved in tribological rehydration. The anticipated results will help reveal why physical activity is so important to joint health while informing ongoing efforts to design the next generation of bio-inspired joint replacement devices. The investigators will recruit local high school seniors to participate in this research through the University of Delaware College of Engineering's K12 Outreach program.Recent in-situ studies of cartilage in a convergent stationary contact area configuration have shown that friction decreases with increased speed, which supports the fluid film theory of joint lubrication. However, they also showed that cartilage simultaneously recovered interstitial fluid, which suggests that hydrodynamic pressures serve to restore hydration (via tribological rehydration) and the interstitial lubrication mechanism. Because existing theory relies on contact migration to expose dehydrated zones to the bath for recovery, the result also implies a fundamentally new mechanism by which joints maintain and recover joint space during activity. By quantifying the effects of physiological articulation amplitudes and contact stresses on passive and active recovery of cartilage, directly interrogating the interfacial and interstitial microfluidics associated with active-rehydration via in-situ confocal microscopy, and evaluating the influence of cartilage degradation on the rehydration of cartilage, this study aims to identify the limits of passive recovery and tribological rehydration in the physiological context and elucidate the mechanism underlying tribological rehydration. The anticipated results of this study will provide new insights into joint mechanics, disease etiology, and the design of new bio-inspired joint replacement systems.

在生理接触压力下，关节间隙薄如间质液体从关节软骨中被驱离。由于软骨的机械和润滑功能依赖于间质液体，不平衡的渗出必然会导致摩擦增加、软骨磨损和关节疾病。幸运的是，由于健康关节间质液体的恢复，软骨和关节间隙实际上在体育活动中变厚了。对于这种恢复，唯一被接受的假说是，“脱水”的软骨区域通过接触迁移而暴露在浴缸中时，被动地摄取液体。然而，最近的现场研究表明，活性诱导的恢复与体内观察到的恢复相当，而不需要接触到浴液；这种现象被称为摩擦学再水化，因为它是由滑动而不是迁移引起的。这些初步结果表明，活动关节间质液体丢失和恢复之间的平衡受到间质(软骨内)和流体动力(软骨之间)压力场的相互作用的调节。本研究通过外植体摩擦学实验和原位共聚焦成像来验证这一假说，以阐明摩擦学再水化的机制。预期的结果将有助于揭示为什么体育活动对关节健康如此重要，同时为正在进行的设计下一代生物灵感关节置换设备的努力提供信息。研究人员将通过特拉华大学工程学院的K12外联计划招募当地高中高年级学生参与这项研究。最近对收敛的固定接触区域配置中的软骨进行的现场研究表明，摩擦力随着速度的增加而减少，这支持关节润滑的流体膜理论。然而，他们也表明软骨同时恢复了间质液体，这表明流体动力压力有助于恢复水化(通过摩擦学再水化)和间质润滑机制。由于现有的理论依赖于接触迁移将脱水的区域暴露在浴缸中进行恢复，这一结果也暗示了一种全新的机制，关节在活动期间通过这种机制维持和恢复关节空间。通过量化生理关节振幅和接触应力对软骨被动和主动恢复的影响，通过原位共聚焦显微镜直接检测与主动再水化相关的界面和间质微流体，以及评估软骨降解对软骨再水化的影响，本研究旨在确定生理环境下被动恢复和摩擦学再水化的极限，并阐明摩擦学再水化的机制。这项研究的预期结果将为关节力学、疾病病因和新的生物灵感关节置换系统的设计提供新的见解。

项目成果

Detrimental effects of long sedentary bouts on the biomechanical response of cartilage to sliding

长时间久坐对软骨滑动生物力学反应的不利影响

• DOI: 10.1080/03008207.2019.1673382
• 发表时间: 2020
• 期刊: Connective Tissue Research
• 影响因子: 2.9
• 作者: Graham, Brian T.;Moore, Axel C.;Burris, David L.;Price, Christopher
• 通讯作者: Price, Christopher

Translational cartilage tribology: How close are we to physiologically relevant benchtop articular cartilage testing?

转化软骨摩擦学：我们距离生理相关的台式关节软骨测试有多远？

• 发表时间: 2020
• 期刊: Tribology lubrication technology
• 作者: Farnham, Margot S;Price, Christopher
• 通讯作者: Price, Christopher

The Effects of Friction in the Presence and Absence of Tribological Rehydration on Chondrocyte Health.

存在和不存在摩擦补液时的摩擦对软骨细胞健康的影响。

• 发表时间: 2019
• 期刊: and Biotransport Conference (SB3C
• 作者: Farnham, MS;Ortved, KF;Schaer, TP;Burris, DL;Price, C
• 通讯作者: Price, C

Quantifying Solute Diffusivity in Human Osteoarthritic Cartilage via Correlation Spectroscopy.

通过相关光谱量化人类骨关节炎软骨中的溶质扩散率。

• 发表时间: 2018
• 期刊: Annual Meeting of the Biomedical Engineering Society (BMES
• 作者: Wright, AD;Graham, BT;Price, C
• 通讯作者: Price, C

Injurious Impaction to Articular Cartilage Does Not Inhibit Biomechanical Outcomes.

对关节软骨的伤害性冲击不会抑制生物力学结果。

• 发表时间: 2018
• 期刊: Annual Meeting of the Biomedical Engineering Society (BMES
• 作者: Larson, R;Farnham, MS;Burris, DL;Price, C
• 通讯作者: Price, C