(D-147) Effects of Hyaluronic Acid on the Lubrication of Degraded Articular Cartilage Under Biofidelic Sliding Conditions

Osteoarthritic degeneration of articular joints is characterized by progressive changes to cartilage’s mechanical properties, including loss of compressive modulus and increased permeability [1]. Such changes have been traditionally viewed as de facto compromisers of tissue function, especially cartilage lubrication [2]. However, our lab has shown that, under the more biofidelic sliding conditions supported by our novel convergent stationary contact area (cSCA) cartilage testing configuration–e.g., high fluid load support (FLS) and high sliding speeds–that modest, osteoarthritis-like degradation of cartilage has, surprisingly, no impact on the tissue’s “natural” lubricating ability–either in saline or synovial fluid (SF) [3].

SF is composed of several macromolecules thought to influence cartilage lubrication [4,5]. One is hyaluronic acid (HA), a high-molecular weight glycosaminoglycan ( >7MDa) found at 1-3mg/mL [6]. Recently, we’ve shown that HA, which is also the major component of current visco-supplementation therapeutics, can lubricate healthy cSCA cartilage similar to SF across a range of FLS and sliding speeds [7]. However, a comprehensive study of the impact of HA alone on the lubrication of degraded cartilage, across sliding speeds and FLS ranging from biofidelic to non-physiological, has yet to be performed. The objective of the study was to leverage the cSCA’s ability to test cartilage across a range of clinically/mechanistically-informative sliding conditions to investigate the lubricating effect of HA–compared to saline–in healthy vs. enzymatically-degraded bovine cartilage. Such studies will better inform the tribomechanical function of healthy vs. osteoarthritic cartilage and the true mechanistic utility of HA-based tribo-supplementation approaches in osteoarthritis.

Results: Exposure to collagenase for 2-hours resulted in mechanical properties consistent with human OA cartilage (ICRS 1-2) [9]. Significant changes in compressive modulus (Ey-; from ∼0.66 to ∼0.25MPa) and permeability (k0; from ∼0.0023 to ∼0.0045mm4/Ns), but not tensile modulus (Ey+) were observed (Fig 1). 

As expected, minimum cSCA equilibrium frictions (𝞵Eq) always occurred at >40mm/s and maximum 𝞵Eq at < 20mm/s, regardless of lubricant or tissue status (Fig 2A). At slow sliding speeds, degradation had no effect on 𝞵Eq in PBS (Fig 2B). Under 10mm/s sliding, HA did not influence healthy cartilage 𝞵Eq (compared to PBS), but led to non-significant 𝞵Eq decrease in degraded cartilage. Under 80mm/s sliding, degraded cartilage exhibited modestly-higher 𝞵Eq in PBS than healthy samples, but not in HA (Fig 2C). Indeed, at 80mm/s, HA reduced 𝞵Eq by >8-fold (vs. PBS) and ~40-fold (vs. 10mm/s) in all tissues. Data collection will continue, up to n=6/group, to appropriately power this dataset.

Discussion: Like in prior studies, brief enzymatic degradation drove clinically-relevant, osteoarthritic-like material property “compromise”. Absent tribological rehydration, i.e., at slow sliding speeds, 𝞵Eq is markedly higher (~0.2, PBS) than if rehydration is present (~0.05; 80mm/s in PBS), and HA provides no frictional benefit to healthy cartilage at slow sliding speeds. With modest osteoarthritic degeneration, HA supports very-limited 𝞵Eq reductions at slow-speeds (~0.09). Degraded tissue’s increased k0 with HA’s water imbibing characteristics may slightly enhance “boundary lubrication” in osteoarthritic cartilage. However, when tribological rehydration maintains high FLS at biofidelic sliding speeds (80mm/s), remarkable 𝞵Eq suppression is seen (~0.005). Indeed, HA supports vanishingly low benchtop 𝞵Eq (matching in vivo predictions) in both healthy and degraded cartilage due to synergistic lubrication. Thus, at biofidelic sliding speeds, lubrication ability is dominated not by degradation status, but by HA (or SF) presence. 

Our study again highlights the importance of synergy between activity-mediated tribological rehydration/FLS recovery and HA-presence in driving robust lubrication in both healthy and osteoarthritis-like cartilage–a key finding in advancing knowledge of how articular cartilage works.