PROGRAM | Mechanical Engineering

By: Shamimur Akanda Chair: Christopher Price

ABSTRACT

The prevalence of the most common form of degenerative joint disease, osteoarthritis (OA), has markedly increased in the latter half of the 20^th century in the United States. It is thought that risk factors endemic to our modern way of living, such as high levels of obesity and physical inactivity, are primary drivers of this  increase in OA prevalence. Besides these—modifiable—behavioral risk factors, aspects of the joint environment are also known to change upon disease initiation that may further accelerate OA progression. Thus, to better understand OA pathoetiology it is crucial to understand the effects of obesity, physical inactivity, and the altered joint environment on the functionality of articular cartilage. Articular cartilage, the exceptionally resilient bearing tissue of our joint, maintains very low friction coefficients over decades of joint articulation. However, in the event of OA, this tissue faces significant structural as well as biological challenges. While studies have investigated the molecular and biological effects of obesity, physical inactivity, and aspects of the altered joint environment (such as synovial fluid [SF] composition) on cartilage homeostasis, the physical effects of these changes on the tribomechanics and lubricating ability of the tissue, its key functional measure, has seen scant attention. Thus, the critical questions regarding the mechanistic impact of these OA risk factors on cartilage function remain unanswered, due in large part to the historical absence of a cartilage tribology testing configuration that biofidelically replicated the in vivo tribomechanics of articular cartilage during normal joint articulation.

This dissertation leveraged the recently rediscovered convergent stationary contact area configuration (cSCA), which supports the sliding driven mechanism termed ‘tribological rehydration’ to both generate and maintain a benchtop lubricating environment over the long-term that is truly biofidelic to the sliding/lubrication conditions cartilage experiences in vivo. Using this novel platform, I investigated (1) how obesity mimicking elevated contact stress influence cartilage rehydration and the tissues native lubrication mechanisms, (2) how varying degrees of obesity-like overloading and sedentary daily inactivity interact to compromise cartilage’s tribomechanical functionality, and how (3a) external bath osmolarity and (3b) OA-mimicking synovial fluid compromise impair cartilage tribomechanics and lubrication.

First (aim 1), I studied the effect of modestly elevated contact stresses—mimicking the effect of obesity—on the tribological rehydration and lubricity of ovine cSCA explants using several experimental approaches. From this work I observed a clear increase in the accumulation of tissue compression as contact stresses increased, accompanied by a total suppression of sliding-driven rehydration at modestly elevated contact stresses (>0.5MPa). However, I found no appreciable effect of contact stress—up to ~0.8MPa—on the tissue’s remarkable lubricity in the cSCA. I also demonstrated that stiffer cartilage—within a narrow range of material properties—better sustains rehydration capability under elevated contact stress.

Next (aim 2), I extended our inquiry of the effect of elevated contact stress on cartilage tribology to include the application of various sedentary vs. active sliding structures to study the effect of obesity and in vivo movement behaviors on cartilage tribomechanics. To approximate the dynamics of daily human loading/movement environment on the benchtop, cSCA studies were temporally scaled to model critical aspects of human movement that are encountered throughout the day, including static loading (e.g., sitting/standing), joint articulation (e.g., walking), and passive unloading (e.g., overnight rest). Within this simulated benchtop ‘day’, activity structures (i.e., intermittent sliding bout number, frequency, and volumes) were varied to model a range of in vivo behaviors, from highly-sedentary to highly-active. From my studies, a key observation was that when applied loads were tripled (resulting in a doubling of contact pressure), tissue strains were found to double, and did so in a manner irrespective of the frequency of structured activity across the day (for a fixed activity volume). Furthermore, increasing daily activity volume by 50%, to almost half of the waking day, was unable to meaningfully mitigate the detrimental consequences of modestly elevated contact stresses on tissue strain accumulation. However, like the previous study, observed minimal effect of contact stress and inactivity on cartilage equilibrium lubrication behaviors. Thus, the present data suggests that articular cartilage lubrication appears quite insensitive to average contact stress and activity patterning. However, cartilage strain, which is a well-established driver of chondrocyte dysfunction, is highly sensitive to contact stress and activity structure, and thus a likely cause of joint dysfunction. Together, these data empirically support the interpretation that limiting contact stress and decreasing inactive/sedentary behaviors are required to sustain cartilage function, and likely tissue health/longevity.

Finally, I explored how (aim 3a) external bath osmolarity, a mediator of tissue intrinsic material properties and swelling behavior, and (aim 3b) OA-like compromise of synovial fluid, the natural bathing material of articular cartilage, influence tissue lubrication and sliding mediated rehydration. Interestingly, studies on cSCA cartilage tested in bathing solutions of varying osmolarity (from hypoosmotic to hyperosmotic) illustrated non-trivial impacts of Donnan osmotic swelling and tissue stiffness on lubrication behavior of the tissue. Most importantly, cSCA explants osmotically “stiffened” by free-swelling in a severely hypoosmotic bathing solution demonstrated dramatically impaired lubricating ability despite persistent tribological rehydration, in contrast, severely hyperosmotically “softened” cartilage retained outstanding lubrication capacity despite compromise of tribological rehydration. These results have begun to provide new insight into the mechanisms underpinning articular cartilages unmatched lubricity. However, because the aforementioned tests were performed under physiologically un-realistic conditions, I next sought to investigate the effects of more biofidelic OA-like compromise of synovial fluid (e.g., dilution and digestion to alter its osmolarity, viscosity, etc.) on cartilage tribomechanics and lubrication. Interestingly, this study observed minimal, and mechanistically insignificant, alterations in the lubricating ability of disease-mimicking synovial fluid in the cSCA . Such findings cast a substantial doubt on the common wisdom that OA-like synovial fluid is an inherently inferior lubricant.

Collectively these studies demonstrated how modifiable risk factors, such as obesity, inactivity, etc. and OA joint environment affect cartilage tribomechanics and lubrication. It has become apparent that tissue compression/strain, not lubrication, may be the primary target of consequence when cartilage tissues in the joint are exposed to OA-associated behavioral risk factors such as obesity (i.e., elevated contact stresses) and inactivity (i.e., increased sedentariness). Furthermore, findings of dramatic impairment of lubrication in osmotically stiffened cSCA explants paves the way for better understanding of cartilage’s native lubrication mechanisms.

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