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，关节间隙变薄，因为间质液从关节软骨中排出。由于软骨依赖于间质液的机械和润滑功能，不平衡的渗出必然导致摩擦增加，软骨磨损和关节疾病。幸运的是，由于健康关节中间质液的恢复，软骨和关节空间在体力活动期间实际上是膨胀的。对于这种恢复的唯一且被接受的假设是，“脱水”软骨区域在通过接触迁移暴露于浴中时被动地吸收流体。然而，最近的原位研究表明，活动诱导的恢复与体内观察到的恢复相当，而没有接触浴;这种现象被称为“摩擦再水化”，因为它是由滑动而不是迁移引起的。这些初步结果表明，间质流体损失和恢复之间的平衡，在活跃的关节调节间质（软骨内）和流体动力学（软骨之间）的压力场之间的相互作用。本研究使用外植体摩擦学实验与原位共聚焦成像来验证这一假设，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身体活动对关节健康如此重要，同时为设计下一代生物启发关节置换设备的持续努力提供信息。 研究人员将通过特拉华州大学工程学院的K12外展项目招募当地高中高年级学生参与这项研究。最近对收敛固定接触区域配置中的软骨进行的原位研究表明，摩擦力随着速度的增加而降低，这支持了关节润滑的流体膜理论。然而，他们还表明软骨同时恢复了间质液，这表明流体动力学压力有助于恢复水合作用（通过摩擦再水合）和间质润滑机制。由于现有的理论依赖于接触迁移，使脱水区暴露于浴中进行恢复，因此该结果也意味着一种全新的机制，通过该机制，关节在活动期间保持和恢复关节空间。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询问与主动再水化相关的界面和间质微流体，并评估软骨降解对软骨再水化的影响，本研究的目的是确定在生理背景下的被动恢复和摩擦学再水化的限制，并阐明摩擦学再水化的潜在机制。这项研究的预期结果将为关节力学、疾病病因学和新型生物启发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