Hydrodynamic lubrication at last: modulation of cartilage superlubricity by articulation speed, lubricant, and tissue properties

Abstract

Articular cartilage is a phenomenal biological bearing material, easily sustaining friction coefficients (μ) <0.005 in vivo; surpassing the criterion for superlubricity (i.e., μ<0.01). This amazing lubricity has been attributed to various mechanisms dependent upon cartilage’s unique structure (i.e., interstitial lubrication) and/or its bathing (synovial) fluid (SF) (i.e., boundary lubrication vs. hydrodynamic lubrication). However, the true basis of cartilage’s remarkable natural lubricity has yet to be established, in part because sustained cartilage superlubricity has only been recently replicated on the benchtop. Only in the last 5 years, with the redeployment of i) the convergent stationary contact area (cSCA) testing configuration coupled with testing ii) under physiologically relevant sliding speeds (e.g., >60mm/s, which promote interfacial hydrodynamics) and iii) in the presence of synovial fluid, have truly in vivo-like μ (<0.004) been demonstrated to be easily sustainable on the benchtop. ☐ Given the transformative advances in our understanding of biofidelic cartilage lubricity that have been enabled by the cSCA configuration, this dissertation aimed to precisely determine the mechanism(s) underlying cartilage superlubricity in the cSCA by establishing the relationship(s) between superlubricity (i.e., μ < 0.01) and sliding speed, lubricant choice and rheological behaviors, and cartilage mechanical properties. Thus, my objectives were: (1) to examine the influence of cartilage explant testing configuration and sliding speed on superlubricity outcomes; determine how SF presence promotes cartilage superlubricity (on the benchtop) via interrogation of the impact of (2) individual SF constituents and (3) non-SF-derived lubricants of shear-thinning behaviors and/or viscosities comparable to SF on cSCA lubrication, and (4) investigate whether, and how, cartilage mechanical properties alter these superlubricity behaviors. ☐ First, I established baseline sliding speed and testing configuration-dependent tribological behaviors with regards to the measured lubricity of articular cartilage explants—ex vivo (Aim 1 – Chapter 2). This work demonstrates that the selection of explant testing configuration and sliding speeds appears to be the strongest determinant of lubricant-dependent coefficients of friction in the tissue and validated that superlubricity on the benchtop is only supported by the rapid sliding of cSCA explants within a synovial fluid bath. Next, I interrogated the role of lubricant choice in mediating cartilage superlubricity outcomes by identifying, in isolation, the SF constituent—at physiological compositions—that replicates these behaviors, showing that hyaluronic acid is the sole constituent of SF necessary and sufficient for promoting/modulating superlubricity in the cSCA (Aim 1 – Chapter 3). Furthermore, I extended this interrogation of lubricant choice by leveraging non-physiological lubricant compositions—having comparable rheological behaviors to SF and hyaluronic acid-based fluids—to determine that lubricant viscosity, rather than presence of a specific macromolecular species, regulates superlubricity within the cSCA (Aim 2 – Chapter 4). Finally, I examined the influence of tissue mechanical properties and the ability of cartilage tissue to generate varying levels of fluid load support (titrated through tonicity) on the capacity of articular cartilage to support superlubricity, revealing that cartilage properties—across the range investigated—had minimal effect on cartilage ability to generate superlubricating behaviors on the benchtop, confirming the robustness of cSCA cartilage’s biofidelic lubrication behaviors (Aim 3 – Chapter 6). ☐ Collectively, these results comprehensively establish key/fundamental relationships among sliding speed, lubricant properties, and tissue mechanical properties that regulate/influence articular cartilage’s ability to approach and exceed the threshold for superlubricating operation on the benchtop, which we infer can be extended to the tissues in situ/in vivo operation. Furthermore, utilizing the expansive dataset collected that I collected for a Stribeck curve-based analysis of μ (Chapter 5), I have shown that articular cartilage lubrication broadly conforms to the well-established behaviors of classical engineered bearings. Such data indicates that despite its complex structure and (biphasic) composition, cartilage does not appear to be an inherently unique bearing material, as it functions nearly identically to that of classically understood engineered bearings when the tissue’s full operational environment is accounted for/explored. These findings will serve to transform the understanding of cartilage’s biofidelic lubricity and, for the first time, present direct evidence of full spectrum lubrication regimes that articular cartilage is capable of supporting/leveraging, including that of the oft debated and dismissed mechanism of hydrodynamic-mediated lubrication. This work, conducted nearly a century after the earliest experiments on cartilage lubrication, brings us full circle to the foundational theories of cartilage lubricity—and moves us significantly closer to finally answering the fundamental question of how cartilage truly works.