PROGRAM | Biomedical Engineering

By: Meghan Kupratis Chair: Christopher Price

ABSTRACT

Articular cartilage functions primarily as a near-frictionless bearing surface that facilitates smooth joint articulation under the varying mechanical demands of activities of daily living. For the better part of a century, ex vivo approaches have failed to replicate the phenomenally low equilibrium friction coefficients (µ_k-eq) measured during articulation of whole joints (<0.005). In contrast, the lowest reported µ_k-eq values from classical explant studies exceed 0.01. Our group attributes these failings to two critical shortcomings: (1) reliance on testing configurations that minimize contributions from fluid flow and (2) emphasis on unrealistically slow sliding speeds (<10mm/s). In vivo, interstitial fluid pressure and flow are critical to cartilage’s mechanical and biological functions. Similarly, joints regularly experience sliding speeds >100mm/s during activities of daily living. Form these observations, it is clear that our incomplete understanding of  cartilage’s tribomechanical function will persist absent appropriate testing strategies that recapitulate joints in vivo usage conditions.

This dissertation leverages the novel convergent stationary contact area (cSCA) testing configuration to examine how tissue-scale mechanical properties inform cartilage’s tribomechanical function in health and disease. The cSCA is the only benchtop testing configuration that models the operating conditions cartilage experiences in vivo—namely, physiological sliding speeds and dynamic fluid load support (FLS)—through a new sliding-driven lubrication mechanism called tribological rehydration. Consequently, the cSCA is also the only configuration that sustains biofidelic friction coefficients in explants. Thus, our objectives were to use the cSCA to investigate (1) whether, and to what extent, variation in the mechanical properties of healthy cartilage influences sliding-mediated tribological rehydration; (2) if tribological rehydration and lubricity are impaired in OA-like cartilage; and (3) how proposed cartilage “reinforcement” techniques influence tribomechanical function.

First, we used a comparative approach to interrogate relationships between cartilage biphasic mechanical properties and cSCA tribomechanics (Aim 1). This work demonstrates the conservation and reproducibility of tribological rehydration in articular cartilage across mammalian species and reveals diverging associations between mechanical properties and tribomechanics depending upon the degree of FLS in the tissue. Next, we extended our interrogation of these relationships to a model of OA-like cartilage generated through enzymatic digestion, revealing that pathological mechanical changes (i.e. softening, elevated permeability) do not compromise tribological rehydration or lubricity in the cSCA (Aim 2). Finally, we examined how collagen crosslinking agents that have been proposed for “reinforcement” of degenerative cartilage or xenogeneic joint resurfacing materials influence cartilage tribomechanics during biofidelic sliding (Aim 3). Although these agents significantly increase tissue stiffness, they also lead to damagingly high friction coefficients, despite persistent tribological rehydration.

Collectively, these results demonstrate that mechanical properties (i.e., stiffness) are incomplete metrics of cartilage function. Furthermore, the marked impairment in lubrication observed after collagen crosslinking underscores the necessity of leveraging biofidelic tribomechanical testing in the design of suitable structurally-modifying treatments for articular cartilage. These findings are transformative to our understanding of cartilage’s natural function in physiological sliding environments and will be critical to future translational research aimed at slowing or preventing cartilage degeneration.

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