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Tribological rehydration of cartilage and its potential role in preserving joint health

  • A.C. Moore
    Affiliations
    Department of Biomedical Engineering, University of Delaware, Newark, DE, USA
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  • D.L. Burris
    Correspondence
    Address correspondence and reprint requests to: D.L. Burris, Department of Biomedical Engineering, University of Delaware, Newark, DE, USA.
    Affiliations
    Department of Biomedical Engineering, University of Delaware, Newark, DE, USA

    Department of Mechanical Engineering, University of Delaware, Newark, DE, USA
    Search for articles by this author
Open ArchivePublished:September 29, 2016DOI:https://doi.org/10.1016/j.joca.2016.09.018

      Summary

      Objective

      During exercise, cartilage recovers interstitial fluid lost during inactivity, which explains how tissue thickness and joint space are maintained over time. This recovery phenomenon is currently explained by a combination of osmotic swelling during intermittent bath exposure and sub-ambient pressurization during unloading. This paper tests an alternate hypothesis that cartilage can retain and recover interstitial fluid in the absence of bath exposure and unloading when physiological hydrodynamics are present.

      Method

      Stationary cartilage-on-flat experiments were conducted to eliminate intermittent bath exposure as a potential contributor to fluid uptake. In situ compression measurements were used to monitor the loss, retention, and recovery of interstitial fluid during testing in saline. Samples were left larger than the contact area to preserve a convergence zone for hydrodynamic pressurization.

      Results

      Interstitial fluid lost during static loading was recovered during sliding in the absence of unloading and contact migration; fluid recovery in a stationary contact cannot be explained by biphasic theory and suggests a fundamentally new contributor to the recovery process. We call the phenomenon ‘tribological rehydration’ because recovery was induced by sliding rather than by unloading or migration. Sensitivities to sliding speed, surface permeability, and nature of the convergence wedge are consistent with the hypothesis that hydrodynamic effects underlie the tribological rehydration phenomenon.

      Conclusions

      This study demonstrates that cartilage can retain and recover interstitial fluid without migration or unloading. The results suggest that hydrodynamic effects in the joint are not only important contributors to lubrication, they are likely equally important to the preservation of joint space.

      Keywords

      Introduction

      The tribological properties of cartilage, the load bearing material in diarthrodial joints, are unrivalled. Its friction coefficient, which is estimated to range from 0.005 and 0.02
      • Charnley J.
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      under physiological conditions, is at least an order of magnitude lower than that of Teflon
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      The frictional properties of animal joints.
      . It has a compression modulus of 0.5 MPa, yet carries 1–5 MPa of contact stress; cartilage routinely carries ∼1000× more stress per unit modulus than bearing steels. Whereas hydrogels, near frictionless carbons, and a few other specialized tribo-materials exhibit comparable super-lubricity
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      Gong JP, Kurokawa T, Narita T, Kagata G, Osada Y, Nishimura G, et al. Synthesis of hydrogels with extremely low surface friction. J Am Chem Soc. doi:10.1021/ja003794q.

      , no material to our knowledge has proven capable of comparable stress capacity.
      These remarkable load-carrying and lubrication properties of cartilage are attributable to its unique biphasic structure
      • McCutchen C.W.
      The frictional properties of animal joints.
      • Armstrong C.G.
      • Lai W.M.
      • Mow V.C.
      An analysis of the unconfined compression of articular-cartilage.
      • Oloyede A.
      • Broom N d
      The generalized consolidation of articular cartilage: an investigation of its near-physiological response to static load.
      . Cartilage comprises approximately 80% water, an organized collagenous scaffold, charged glycosaminoglycans, and cells. Under load, the interstitial fluid pressurizes against the collagenous scaffold and, as Amstrong et al. first showed, preferentially carries the bulk of the contact force to shield the matrix from stress
      • Armstrong C.G.
      • Lai W.M.
      • Mow V.C.
      An analysis of the unconfined compression of articular-cartilage.
      ; it is for this reason that joint strains are so small despite the large contact stress per unit compression modulus. Although these interstitial pressures support load, they also drive fluid from the tissue, which results in increased strain, reduced water content, and decreased fluid pressure as the tissue approaches a mechanical equilibrium
      • Krishnan R.
      • Kopacz M.
      • Ateshian G.A.
      Experimental verification of the role of interstitial fluid pressurization in cartilage lubrication.
      .
      Joint space narrowing, defined by the abnormal approach of opposing bones of a joint, is a reliable clinical indicator of joint disease
      • Fife R.S.
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      Relationship between arthroscopic evidence of cartilage damage and radiographic evidence of joint space narrowing in early osteoarthritis of the knee.
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      . Although joint space narrowing is generally attributed to wear of the articular cartilage
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      • Shelburne K.D.
      • Kalasinski L.A.
      • et al.
      Relationship between arthroscopic evidence of cartilage damage and radiographic evidence of joint space narrowing in early osteoarthritis of the knee.
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      • et al.
      Risk factors for the incidence and progression of radiographic knee osteoarthritis.
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      Exercise and osteoarthritis.
      it also results from the exudation of interstitial fluid
      • Eckstein F.
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      • Faber S.
      • Englmeier K.H.
      • Reiser M.
      Functional analysis of articular cartilage deformation, recovery, and fluid flow following dynamic exercise in vivo.
      . Eckstein et al. used MRI to demonstrate that healthy joints maintain strains below ∼10% during exercise
      • Eckstein F.
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      • Faber S.
      • Englmeier K.H.
      • Reiser M.
      Functional analysis of articular cartilage deformation, recovery, and fluid flow following dynamic exercise in vivo.
      , which appears at odds with predictions from biphasic theory and measurements on loaded cartilage explants
      • McCutchen C.W.
      The frictional properties of animal joints.
      • Armstrong C.G.
      • Lai W.M.
      • Mow V.C.
      An analysis of the unconfined compression of articular-cartilage.
      • Krishnan R.
      • Kopacz M.
      • Ateshian G.A.
      Experimental verification of the role of interstitial fluid pressurization in cartilage lubrication.
      . However, Ateshian and Wang showed that interstitial fluid and interstitial pressure can be maintained in the joint if the contact area continuously moves to new hydrated locations of cartilage faster than the interstitial fluid at any one location could respond
      • Ateshian G.A.
      • Wang H.Q.
      A theoretical solution for the frictionless rolling-contact of cylindrical biphasic articular-cartilage layers.
      ; such situations are called migrating contact areas (MCAs)
      • Caligaris M.
      • Ateshian G.A.
      Effects of sustained interstitial fluid pressurization under migrating contact area, and boundary lubrication by synovial fluid, on cartilage friction.
      . Caligaris and Ateshian later demonstrated the phenomenon experimentally by showing that interstitial pressure was maintained when a small glass sphere slid against cartilage
      • Caligaris M.
      • Ateshian G.A.
      Effects of sustained interstitial fluid pressurization under migrating contact area, and boundary lubrication by synovial fluid, on cartilage friction.
      .
      Whereas joint activity maintains tissue function and hydration, static contact (sitting, standing) leads to load-driven exudation. Herberhold et al. showed that just a few hours of inactivity may lead to joint strains in excess of 50%
      • Herberhold C.
      • Faber S.
      • Stammberger T.
      • Steinlechner M.
      • Putz R.
      • Englmeier K.H.
      • et al.
      In situ measurement of articular cartilage deformation in intact femoropatellar joints under static loading.
      . Fortunately, Ingelmark and Ekholm showed that human joints recover interstitial fluid and thicken during activity after inactivity
      • Ekholm R.
      • Ingelmark B.E.
      Functional thickness variations of human articular cartilage.
      • Ingelmark B.E.
      • Ekholm R.
      A study on variations in the thickness of articular cartilage in association with rest and periodical load; an experimental investigation on rabbits.
      . Their findings demonstrate that activity prevents joint space narrowing by reversing the inactivity-driven exudation and thinning processes. Linn made similar observations using ex-vivo measurements of canine ankles
      • Linn F.C.
      Lubrication of animal joints.
      and pointed out that fluid is naturally recovered via osmotic swelling when the dehydrated portion of the surface becomes exposed to the bath during articulation; Ingelmark and Ekholm and McCutchen previously described similar lines of reasoning
      • McCutchen C.W.
      The frictional properties of animal joints.
      • Ekholm R.
      • Ingelmark B.E.
      Functional thickness variations of human articular cartilage.
      • Ingelmark B.E.
      • Ekholm R.
      A study on variations in the thickness of articular cartilage in association with rest and periodical load; an experimental investigation on rabbits.
      .
      Based on existing literature, joint space and interstitial fluid are preserved and restored because contact migration (joint activity) provides insufficient time for fluid exudation and intermittently exposes the contact to the bath
      • Mow V.C.
      • Holmes M.H.
      • Michael Lai W.
      Fluid transport and mechanical properties of articular cartilage: a review.
      . Loaded contacts that remain stationary relative to the cartilage, so-called stationary contact areas (SCAs), lack these attributes and are presumed to lose interstitial fluid, pressure, lubrication, and thickness over time
      • Rajan V.
      • Caligaris M.
      • Hung C.T.
      • Ahmad C.S.
      • Ateshian G.A.
      Hemiarthroplasties defeat interstitial fluid pressurization in cartilage and promote greater friction than natural joints.
      • Oungoulian S.R.
      • Durney K.M.
      • Jones B.K.
      • Ahmad C.S.
      • Hung C.T.
      • Ateshian G.A.
      Wear and damage of articular cartilage with friction against orthopedic implant materials.
      as evidenced theoretically and experimentally
      • Krishnan R.
      • Kopacz M.
      • Ateshian G.A.
      Experimental verification of the role of interstitial fluid pressurization in cartilage lubrication.
      • Park S.H.
      • Krishnan R.
      • Nicoll S.B.
      • Ateshian G.A.
      Cartilage interstitial fluid load support in unconfined compression.
      • Forster H.
      • Fisher J.
      The influence of loading time and lubricant on the friction of articular cartilage.
      • Pawaskar S.S.
      • Jin Z.M.
      • Fisher J.
      Modelling of fluid support inside articular cartilage during sliding.
      . However, in our preliminary investigations into a potential interaction between the fluid film
      • Wright V.
      • Dowson D.
      Lubrication and cartilage.
      and interstitial theories of joint lubrication
      • Ateshian G.A.
      The role of interstitial fluid pressurization in articular cartilage lubrication.
      , we observed clear evidence that cartilage had retained and recovered interstitial fluid during sliding without the benefit of contact migration or unloading; because the phenomenon was sliding-induced rather than unloading-induced or migration-induced, we call it ‘tribological rehydration’. Here we aim to disseminate the discovery of tribological rehydration, probe the conditions under which tribological rehydration occurs, establish a feasible conceptual framework that describes the underlying mechanics, and assess the likelihood with which tribological rehydration contributes to the retention and recovery of joint space in vivo.

      Materials and methods

      Specimens

      Twenty-six samples from seven mature bovine stifles were used in this study. Osteochondral cores (19 mm diameter) were removed from the femoral condyle, rinsed, and stored in phosphate buffered saline (PBS). Following a 1+ hour soak in PBS the test sample was removed and clamped via the bone. Samples not tested immediately were placed in a laboratory refrigerator at 4°C for no more than 4 days, a duration insufficient to cause detectable changes in properties
      • Moore A.C.
      • Burris D.L.
      Tribological and material properties for cartilage of and throughout the bovine stifle: support for the altered joint kinematics hypothesis of osteoarthritis.
      .

      In situ tribometer

      A schematic of the in situ tribometer is displayed in Fig. 1. The device is composed of a translation stage and a loading assembly. The translation stage reciprocates a glass microscope slide using a linear actuator (MDrive 14). A linear variable differential transformer (LVDT) (RDP MD5/500AG) was used to track the relative position of the glass slide during reciprocation. The vertical stage was used to load the cartilage sample against the glass slide. A 6-channel load cell (ATI Nano 17: 10 mN resolution) was attached to the base of the sample for normal and friction force measurements and a vertical linear variable differential transformer (RDP GT2500: 100 nm resolution) was used to measure vertical displacements of the sample relative to the counterface (compression).
      Fig. 1
      Fig. 1Schematic of the in situ tribometer used to demonstrate tribological rehydration. a) The in situ tribometer, b) a schematic of the primary operating principles, c) in situ optical view of the contact area between the glass slide and the 19 mm diameter sample. The reciprocating stage moves the glass slide relative to the cartilage at speeds up to 60 mm/s. The loading assembly brings the cartilage into contact with the glass slide under a normal load of 5 N, which typically results in a ∼5 mm contact diameter. We classify the contact as a cSCA when the sample diameter exceeds the contact diameter thereby creating an entrainment zone for hydrodynamic pressurization. An LVDT monitors cartilage compression and a load cell measures normal and friction forces.

      Tribology testing

      Reciprocating cartilage-on-flat (SCA) experiments were used to test tribological rehydration in the absence of contact migration. The situation is equivalent to unconfined compression from the standpoint of biphasic theory and interstitial pressure will drive fluid from the tissue over time regardless of the sliding condition
      • Armstrong C.G.
      • Lai W.M.
      • Mow V.C.
      An analysis of the unconfined compression of articular-cartilage.
      . We sub-classify the setup as a convergent stationary contact area (cSCA) if there exists a convergence zone for hydrodynamic pressurization; this is accomplished naturally when the convex sample size is larger than the contact as shown in Fig. 1(b) and (c). The standard experiment used a track length of 20 mm, a sliding speed of 60 mm/s, and a normal load of 5 N, which corresponded roughly to a contact diameter of 5 ± 0.4 mm and a contact pressure of 0.25 ± 0.05 MPa based on in situ observations of the contact interface [Fig. 1(c)].

      Experimental variations

      Several variations of the standard experiment were conducted to systematically probe hydrodynamic effects. First, the sample was cut with a CNC mill from 19 to 6 mm in diameter in an effort to reduce the size of the entrainment zone and therefore, the hydrodynamic effect. Previous studies demonstrated that such size reductions had no detectable effect on material properties
      • Moore A.C.
      • DeLucca J.F.
      • Burris D.L.
      • Elliott D.M.
      Quantifying cartilage contact modulus, tensile modulus, and permeability with Hertzian biphasic creep.
      ; in addition, direct in situ observations of the contact diameter revealed no significant effect on contact radius or pressure. Sliding speed was reduced to 10 mm/s and 0 mm/s to vary hydrodynamic effects without changing sample geometry. Finally, by drawing an impermeable 10 μm thick polymer membrane over the cartilage to prevent inflow, we were able to isolate the potentially confounding effects of fluid films on the compression response of permeable cartilage.

      Results

      Standard cSCA experiments

      Standard cSCA experiments (60 mm/s, 20 mm track, 5 N load) were conducted on 26 samples from seven independent stifles; the in situ steady state compression and friction statistics are provided in Table I. Cartilage samples maintained low friction coefficients in the cSCA configuration with a mean value of 0.011. Previous SCA studies have shown a ubiquitous transition toward unremarkable steady state friction coefficients in the range of 0.1 to 0.6
      • McCutchen C.W.
      The frictional properties of animal joints.
      • Forster H.
      • Fisher J.
      The influence of loading time and lubricant on the friction of articular cartilage.
      • Basalo I.M.
      • Chen F.H.
      • Hung C.T.
      • Ateshian G.A.
      Frictional response of bovine articular cartilage under creep loading following proteoglycan digestion with chondroitinase ABC.
      • Krishnan R.
      • Caligaris M.
      • Mauck R.L.
      • Hung C.T.
      • Costa K.D.
      • Ateshian G.A.
      Removal of the superficial zone of bovine articular cartilage does not increase its frictional coefficient.
      • Caligaris M.
      • Canal C.E.
      • Ahmad C.S.
      • Gardner T.R.
      • Ateshian G.A.
      Investigation of the frictional response of osteoarthritic human tibiofemoral joints and the potential beneficial tribological effect of healthy synovial fluid.
      • Schmidt T.A.
      • Gastelum N.S.
      • Nguyen Q.T.
      • Schumacher B.L.
      • Sah R.L.
      Boundary lubrication of articular cartilage – role of synovial fluid constituents.
      . The facts that the present study involved a convergence zone for hydrodynamic pressurization and ∼6× greater sliding speed appears to suggest that the contacts were lubricated by hydrodynamic fluid films
      • Macconaill M.A.
      The function of intra-articular fibrocartilages, with special reference to the knee and inferior radio-ulnar joints.
      • Dowson D.
      • Wright V.
      • Longfield M.D.
      Human joint lubrication.
      . However, these samples compressed to only 0.073 mm during steady state sliding. With an average tissue thickness of 1.3 mm and a mean compression modulus of 0.5 MPa
      • Moore A.C.
      • Burris D.L.
      Tribological and material properties for cartilage of and throughout the bovine stifle: support for the altered joint kinematics hypothesis of osteoarthritis.
      , it is inferred that the mean ‘solid’ (osmotic) stress carried by the tissue was ∼28 kPa at steady state, which is an order of magnitude less than the applied stress. Based on these in situ compression measurements, we can conclude that samples maintained ∼90% fluid load support. These compression measurements demonstrate that interstitial fluid and pressure had been retained without contact migration; the simultaneous retention of low friction coefficient and high fluid load support is consistent with the interstitial hypothesis of joint lubrication
      • Krishnan R.
      • Kopacz M.
      • Ateshian G.A.
      Experimental verification of the role of interstitial fluid pressurization in cartilage lubrication.
      • Ateshian G.A.
      The role of interstitial fluid pressurization in articular cartilage lubrication.
      Table ISteady state mean ± standard deviation of cartilage compression and friction coefficients produced during cSCA experiments with N = 26 samples from the femoral condyles of seven independent bovine stifle joints
      Sliding configurationMeasurementμ ± σN
      cSCACompression (mm)0.073 ± 0.03526
      cSCAFriction coefficient0.011 ± 0.00726

      Transition from cSCA to SCA

      The retention of interstitial pressure in the absence of migration is unexpected based on biphasic theory alone. The key distinctions between these experiments and previous studies are the presence of a convergent wedge and physiological sliding speeds, both of which promote hydrodynamic pressurization. Follow-up experiments were conducted to isolate the effect of the convergent wedge. The friction coefficient (μ) and compression are plotted versus time for a representative sample as a function of explant diameter in Fig. 2. The friction coefficient starts below 0.02 independently of size, which is the expected result
      • McCutchen C.W.
      The frictional properties of animal joints.
      • Caligaris M.
      • Ateshian G.A.
      Effects of sustained interstitial fluid pressurization under migrating contact area, and boundary lubrication by synovial fluid, on cartilage friction.
      • Forster H.
      • Fisher J.
      The influence of loading time and lubricant on the friction of articular cartilage.
      • Basalo I.M.
      • Chen F.H.
      • Hung C.T.
      • Ateshian G.A.
      Frictional response of bovine articular cartilage under creep loading following proteoglycan digestion with chondroitinase ABC.
      • Krishnan R.
      • Caligaris M.
      • Mauck R.L.
      • Hung C.T.
      • Costa K.D.
      • Ateshian G.A.
      Removal of the superficial zone of bovine articular cartilage does not increase its frictional coefficient.
      • Caligaris M.
      • Canal C.E.
      • Ahmad C.S.
      • Gardner T.R.
      • Ateshian G.A.
      Investigation of the frictional response of osteoarthritic human tibiofemoral joints and the potential beneficial tribological effect of healthy synovial fluid.
      • Schmidt T.A.
      • Gastelum N.S.
      • Nguyen Q.T.
      • Schumacher B.L.
      • Sah R.L.
      Boundary lubrication of articular cartilage – role of synovial fluid constituents.
      . At 6 mm diameter, the contact area was approximately equal to the sample area, which effectively eliminated the convergent wedge. Friction increased over time as predicted by biphasic theory and as demonstrated previously for the SCA configuration
      • McCutchen C.W.
      The frictional properties of animal joints.
      • Caligaris M.
      • Ateshian G.A.
      Effects of sustained interstitial fluid pressurization under migrating contact area, and boundary lubrication by synovial fluid, on cartilage friction.
      • Forster H.
      • Fisher J.
      The influence of loading time and lubricant on the friction of articular cartilage.
      • Basalo I.M.
      • Chen F.H.
      • Hung C.T.
      • Ateshian G.A.
      Frictional response of bovine articular cartilage under creep loading following proteoglycan digestion with chondroitinase ABC.
      • Krishnan R.
      • Caligaris M.
      • Mauck R.L.
      • Hung C.T.
      • Costa K.D.
      • Ateshian G.A.
      Removal of the superficial zone of bovine articular cartilage does not increase its frictional coefficient.
      • Caligaris M.
      • Canal C.E.
      • Ahmad C.S.
      • Gardner T.R.
      • Ateshian G.A.
      Investigation of the frictional response of osteoarthritic human tibiofemoral joints and the potential beneficial tribological effect of healthy synovial fluid.
      • Schmidt T.A.
      • Gastelum N.S.
      • Nguyen Q.T.
      • Schumacher B.L.
      • Sah R.L.
      Boundary lubrication of articular cartilage – role of synovial fluid constituents.
      . At 12 and 19 mm diameters, the sample was large enough to provide an entrainment zone (convergent wedge) for hydrodynamic pressurization and, in both cSCA cases, the friction coefficient increased only slightly toward μ = 0.02 at steady state.
      Fig. 2
      Fig. 2(a) Friction coefficient and (b) compression of a single representative cartilage sample cut to varying size (19, 12, 6 mm diameter). A convex shape and large sample size leaves a convergence zone for fluid entrainment and hydrodynamic pressurization as illustrated schematically. When the sample size approached the contact area, friction and compression increased with time as expected for the SCA
      • Charnley J.
      The lubrication of animal joints in relation to surgical reconstruction by arthroplasty.
      . The standard testing configuration (60 mm/s, 20 mm track, 5 N load) was used and PBS lubrication was maintained throughout the experiment.
      Initially the compression rate also appears independent of sample size, which is consistent with biphasic theory [Fig. 2(b)]. The 6 mm size displayed the familiar runaway compression response characteristic of the SCA
      • McCutchen C.W.
      The frictional properties of animal joints.
      ; in this case, the loss of fluid leads to reduced fluid pressure, increased solid load carrying and increased friction over time as previously observed
      • Krishnan R.
      • Kopacz M.
      • Ateshian G.A.
      Experimental verification of the role of interstitial fluid pressurization in cartilage lubrication.
      • Park S.H.
      • Krishnan R.
      • Nicoll S.B.
      • Ateshian G.A.
      Cartilage interstitial fluid load support in unconfined compression.
      • Forster H.
      • Fisher J.
      The influence of loading time and lubricant on the friction of articular cartilage.
      • Pawaskar S.S.
      • Jin Z.M.
      • Fisher J.
      Modelling of fluid support inside articular cartilage during sliding.
      . At larger sizes, the same sample stabilized at a compression of about 60 μm, which is comparable to the mean response we observed for the 26-sample cSCA set. These results suggest that hydrodynamic effects arrested the anticipated fluid exudation process, which is ultimately responsible for increased compression and friction over time.

      Start-stop experiment

      Additional experiments were conducted to elucidate the dynamics of the exudation and recovery processes. A second representative 19 mm diameter sample was slid at 60 mm/s for 600 s and then stopped; the compression of this sample is shown as a function of time in Fig. 3(a). In this case, exudation ceased at a compression asymptote of ∼40 μm during sliding, but resumed as expected once sliding stopped. Following recovery by soaking in PBS, the sample was compressed statically at the same load to obtain the static equilibration response. Comparison against the original test results produced two noteworthy observations. Firstly, the initial compressive response during sliding was identical to the initial response under static loading, which suggests that the competing effects of hydrodynamic pressurization were negligible initially. Only after ∼15 μm of compression did the curves begin diverging, which suggests that significant deformations are required to produce competitive hydrodynamic pressurization; the coupling of deformation and hydrodynamic pressurization is the defining feature of elasto-hydrodynamics or EHD
      • Hamrock B.J.
      • Dowson D.
      Elastohydrodynamic lubrication of elliptical contacts for materials of low elastic-modulus I – fully flooded conjunction.
      . Secondly, the static exudation response following sliding overlays nearly perfectly onto the control equilibration response, indicating the exudation response is strain dependent and history independent. These results suggest that, at dynamic equilibrium, EHD pressurization drives fluid into the surface at a rate equal to the rate of exudation (rather than actually arresting exudation).
      Fig. 3
      Fig. 3(a) Compression of a second representative cartilage sample versus time in a start-stop cSCA test configuration. The sample was loaded to 5 N and slid at 60 mm/s. Reciprocation was stopped at 600 s to provide a period of static equilibration. The sample was then unloaded and soaked for 1 h to restore interstitial fluid and equilibrated again under static conditions at 5 N. (b) Compression and friction versus time for a third representative sample in a stop-start test configuration. Following a period of static equilibration, the sample began sliding at 60 mm/s until reaching a dynamic equilibrium; following equilibration, sliding speed was reduced to 10 mm/s. Both tests were conducted in PBS.

      Stop-start experiment

      Figure 3(b) illustrates the recovery of interstitial fluid following static loading and gross exudation. In this case, a third 19 mm diameter sample was compressed by 90 μm over 600 s of static loading. On the first sliding cycle at 60 mm/s the friction coefficient was μ = 0.16, which clearly indicates an absence of a hydrodynamic fluid film. Thereafter the friction coefficient and compression decreased monotonically with continued cycling, reaching asymptotes of μ ∼0.005 and δ ∼60 μm (∼5% strain), respectively. The correspondence between strain and friction strongly implicates the recovery of interstitial fluid and pressure as the mechanism underlying the friction and strain reductions. Although hydrodynamic pressures are typically associated with fluid film (or mixed) lubrication, it appears that hydrodynamic pressurization acted primarily to restore interstitial hydration by combating the persistent exudation process with competitive inflow.
      Reducing the sliding speed from 60 mm/s to 10 mm/s caused increased compression and friction over time. As the overlay in Fig. 3(b) illustrates, the compression rate at 10 mm/s was less than that under static conditions. This suggests that the driving force for recovery was substantially reduced but not eliminated at the slow speeds typical of SCA measurements
      • Caligaris M.
      • Ateshian G.A.
      Effects of sustained interstitial fluid pressurization under migrating contact area, and boundary lubrication by synovial fluid, on cartilage friction.
      • Forster H.
      • Fisher J.
      The influence of loading time and lubricant on the friction of articular cartilage.
      • Forster H.
      • Fisher J.
      The influence of continuous sliding and subsequent surface wear on the friction of articular cartilage.
      . In general, increased speeds caused thickening and decreased friction, while decreased speeds caused compression and increased friction; this observation is consistent with the hypothesis that load-induced exudation was offset by speed-induced inflow from EHD pressurization, which is strongly speed dependent
      • Hamrock B.J.
      • Dowson D.
      Elastohydrodynamic lubrication of elliptical contacts for materials of low elastic-modulus I – fully flooded conjunction.
      .

      Dynamics of fluid films

      A final set of experiments was conducted to study the mechanics of fluid film formation and collapse. An impermeable membrane was drawn taut over a representative sample to prevent inflow into the articular surface while maintaining the mechanics that drive soft-EHD. PBS (1 mPa-s) lubricant was used to determine the extent to which fluid films contributed to the compression response from the standard cSCA experiment described above; glycerol (1000 mPa-s) lubricant was used to thicken the fluid films and improve resolution for studies of formation and collapse dynamics.
      Figure 4(a) shows that sliding with an impermeable membrane produced a compression response similar to that of static loading of permeable cartilage. The fact that compression was unaltered by the layer indicates that 1) the layer did not significantly alter the biphasic response and 2) frictional shear stresses had no meaningful effect on the exudation response of the tissue as expected from biphasic theory. A slight ‘jump’ in compression occurred when sliding stopped. Although such a jump could be expected due to the coupling of shear strain and compression, the sudden loss of shear strain would decrease not increase compression. This result suggests that a very thin film likely formed during sliding when the cartilage surface was made impermeable. Under PBS lubrication, these films appear to be on the order of 500–1000 nm, which is thin but well above the instrument uncertainty (∼100 nm). Nonetheless, it is clear that the 10's μm compressions and recoveries observed in the standard cSCA experiments (Table I and Fig. 2, Fig. 3) cannot be attributed to variations in fluid film thickness, shear-compression coupling, or wear alone; they can confidently be attributed to the loss and recovery of interstitial fluid, respectively.
      Fig. 4
      Fig. 4(a) Cartilage compression versus time when covered by a thin impermeable polymer film and lubricated by a bath of PBS. Interstitial fluid was isolated from bath fluid by the layer but retained its ability to leave the cartilage sample. Stopping the test produced an abrupt increase in compression, which is consistent with the collapse of a fluid film. (b) Compression versus time over multiple start-stop cycles for the layer-covered (impermeable) sample in a viscous glycerol bath and natural cartilage (permeable) in PBS.
      Repeat impermeable-surface experiments in glycerol better illustrate the dynamics of the fluid film response. In this case, the fluid films were significant with a thickness closer to 7 μm [Fig. 4(b)] due the 1000× larger viscosity of the lubricant. The measured film thickness and immediate formation are both consistent with soft-EHD theory
      • Hamrock B.J.
      • Dowson D.
      Elastohydrodynamic lubrication of elliptical contacts for materials of low elastic-modulus I – fully flooded conjunction.
      • Myant C.
      • Fowell M.
      • Spikes H.A.
      • Stokes J.R.
      • Chang L.
      An investigation of lubricant film thickness in sliding compliant contacts.
      . The fluid films collapsed only slightly slower upon stopping because of the well-known squeeze-film effect
      • Hlavacek M.
      Squeeze-film lubrication of the human ankle joint with synovial fluid filtrated by articular cartilage with the superficial zone worn out.
      .
      In a third cycling experiment the impermeable film was removed to illustrate the marked effect of interface permeability on start-stop-start dynamics. During sliding, the sample approached a strain asymptote of ∼5% suggesting that exudation had been arrested as shown previously. When sliding stopped, exudation resumed. When sliding resumed, fluid was recovered and strain returned to the dynamic asymptote. Cartilage retained interstitial fluid during sliding, lost interstitial fluid when sliding stopped, and gained interstitial fluid when sliding resumed in a repeatable fashion that is consistent with the known response of joint space to changes in physical activity
      • Ekholm R.
      • Ingelmark B.E.
      Functional thickness variations of human articular cartilage.
      . The results strongly suggest that low strain at steady state sliding occurs because load-induced exudation rates have been balanced by competitive speed-induced imbibition rates. We call this imbibition phenomenon tribological rehydration because it is sliding-induced rather than unloading or migration-induced.

      Discussion

      The cSCAs of this study lost, maintained, and recovered compression, lubrication, and fluid during sliding depending on the sliding conditions, contact stress, and strain. The deformations observed cannot be explained by wear, shear-induced compression, or variations in film thickness given the large discrepancy between film thickness and compression (Fig. 4). Therefore, the deformations observed in this study for natural cartilage can primarily be attributed to a competition between the loss and recovery of interstitial fluid by the tissue. As such, this study presents the first direct experimental evidence that interstitial fluid can be retained and recovered in the absence of unloading and contact migration, a result with important scientific and clinical implications to be discussed later. We call this recovery process tribological rehydration because it was sliding-induced rather than unloading or migration-induced.
      The cSCAs in this study produced fluid load fractions, friction coefficients and compressive strains at steady state that were consistent with measurements from previous cartilage explant and whole joint studies. The estimated mean fluid load fraction from this study of ∼90% is comparable with maximum values from unconfined compression measurements of bovine patellofemoral cartilage
      • Park S.H.
      • Krishnan R.
      • Nicoll S.B.
      • Ateshian G.A.
      Cartilage interstitial fluid load support in unconfined compression.
      (94% ± 4% at the articular surface and 71% ± 8% in the deep zone cartilage) and our steady state values from MCA studies of bovine cartilage from the femoral condyle
      • Moore A.C.
      • Burris D.L.
      Tribological and material properties for cartilage of and throughout the bovine stifle: support for the altered joint kinematics hypothesis of osteoarthritis.
      (83% ± 3%). Likewise, the mean friction coefficient from this study (0.011) compares well with those from MCA measurements of Moore and Burris
      • Moore A.C.
      • Burris D.L.
      Tribological and material properties for cartilage of and throughout the bovine stifle: support for the altered joint kinematics hypothesis of osteoarthritis.
      (0.021) and Caligaris and Ateshian
      • Caligaris M.
      • Ateshian G.A.
      Effects of sustained interstitial fluid pressurization under migrating contact area, and boundary lubrication by synovial fluid, on cartilage friction.
      (0.022) as well as those from whole joint measurements of Charnley
      • Charnley J.
      The lubrication of animal joints in relation to surgical reconstruction by arthroplasty.
      (0.013) and Linn
      • Linn F.C.
      Lubrication of animal joints.
      (0.012). The slightly larger values from the MCA measurements are likely the result of an additional plowing component from the smaller probe sizes
      • Bonnevie E.D.
      • Baro V.J.
      • Wang L.Y.
      • Burris D.L.
      In situ studies of cartilage microtribology: roles of speed and contact area.
      . Lastly, and perhaps most interestingly in the context of joint space, the observed compressive strains of ∼5% in this study are comparable to those observed by Eckstein et al.
      • Eckstein F.
      • Tieschky M.
      • Faber S.
      • Englmeier K.H.
      • Reiser M.
      Functional analysis of articular cartilage deformation, recovery, and fluid flow following dynamic exercise in vivo.
      (in vivo, 5–12% during various activities) and Linn
      • Linn F.C.
      Lubrication of animal joints.
      (in situ, 0.1 mm across two surfaces gives ∼5% strain). The remarkable consistencies in these numbers across studies and methods suggest that the mechanics underlying cartilage lubrication are the same in the cSCA, the MCA, and the joint.
      It is not obvious why interstitial pressure would be maintained or recovered in any stationary contact area including those used here. Biphasic theory predicts that interstitial pressure drives exudation and is therefore inherently self-defeating without contact migration
      • Mow V.C.
      • Kuei S.C.
      • Lai W.M.
      • Armstrong C.G.
      Biphasic creep and stress-relaxation of articular-cartilage in compression – theory and experiments.
      . However, this study suggests that the coupling of interstitial and hydrodynamic pressure fields cannot be neglected, as is almost always the case in theoretical analyses of biphasic contacts
      • Ateshian G.A.
      • Wang H.Q.
      A theoretical solution for the frictionless rolling-contact of cylindrical biphasic articular-cartilage layers.
      • Pawaskar S.S.
      • Jin Z.M.
      • Fisher J.
      Modelling of fluid support inside articular cartilage during sliding.
      • Ateshian G.A.
      • Maas S.
      • Weiss J.A.
      Finite element algorithm for frictionless contact of porous permeable media under finite deformation and sliding.
      • Sakai N.
      • Hagihara Y.
      • Furusawa T.
      • Hosoda N.
      • Sawae Y.
      • Murakami T.
      Analysis of biphasic lubrication of articular cartilage loaded by cylindrical indenter.
      • Zhu F.
      • Wang P.
      • Lee N.H.
      • Goldring M.B.
      • Konstantopoulos K.
      Prolonged application of high fluid shear to chondrocytes recapitulates gene expression profiles associated with osteoarthritis.
      • Accardi M.A.
      • Dini D.
      • Cann P.M.
      Experimental and numerical investigation of the behaviour of articular cartilage under shear loading-Interstitial fluid pressurisation and lubrication mechanisms.
      . Theoretical evidence that hydrodynamic pressures develop in the convergence zones of joints suggests to many that low friction coefficients occur because hydrodynamic fluid films separate joint surfaces
      • Macconaill M.A.
      The function of intra-articular fibrocartilages, with special reference to the knee and inferior radio-ulnar joints.
      • Dowson D.
      • Wright V.
      • Longfield M.D.
      Human joint lubrication.
      • Dowson D.
      • Unsworth A.
      • Wright V.
      Analysis of boosted-lubrication in human joints.
      . However, Gleghorn et al.
      • Gleghorn J.P.
      • Bonassar L.J.
      Lubrication mode analysis of articular cartilage using Stribeck surfaces.
      and Ateshain
      • Ateshian G.A.
      The role of interstitial fluid pressurization in articular cartilage lubrication.
      point out that lubricating fluid films in joints are likely compromised by flow into the porous surfaces. This study showed that a thin fluid film did develop when the surface was made to be impermeable [Fig. 4(a)], which supports the hypothesis that EHD pressurization is significant as previous literature suggests
      • Dowson D.
      • Jin Z.-M.
      Micro-elastohydrodynamic lubrication of synovial joints.
      • Dowson D.
      Modes of lubration in human joints.
      . To our knowledge, there have been no theoretical or experimental studies of the interaction between hydrodynamic and interstitial pressure fields. However, it is known that the applied load causes interstitial pressurization within the bulk of the cartilage, which causes bulk exudation; it is also known that relative motion from sliding causes fluid entrainment into a convergent wedge, which leads to rapid pressurization very near the wedge tip
      • Hamrock B.J.
      • Schmid S.R.
      • Jacobson B.O.
      Fundamentals of Fluid Film Lubrication.
      . The simplest mental model of the fluid mechanics based on existing theory suggests a competition between EHD pressure-driven inflow and interstitial pressure-driven outflow. This EHD-based hypothesis for the mechanism underlying the tribological rehydration phenomenon (illustrated in Fig. 5) appears consistent with the present results and well-established literature.
      Fig. 5
      Fig. 5Illustration of the hydrodynamic hypothesis of tribological rehydration. (1) Initial contact and deformation cause maximal pressurization of interstitial fluid, which typically supports 90–99% of the applied load. Interstitial pressure drives flow toward the low pressure bath along paths of least resistance; flow may occur through the tissue, through percolated ‘channels’ formed by contact with the rough cartilage surface, or a combination thereof. (2) Compression increases as interstitial fluid flows, resulting in increased load carrying by the solid, decreased interstitial pressure, and decreased compression rate. (3) Relative motion draws fluid into the convergent wedge where it is subsequently pressurized via EHD and forced into the contacting cartilage surface. As compression decreases, interstitial pressure, especially at the frictional interface, increases resulting in decreased friction and increased exudation rates; (4) the system achieves dynamic equilibrium once the exudation rate matches the imbibition rate. The transition to slower sliding speeds produces decreased EHD pressure, decreased imbibition rate, increased compression rate, and increased friction (5).
      To date, the recovery of interstitial fluid in joints has been attributed to osmotic swelling during intermittent bath exposures within a migrating contact
      • Linn F.C.
      Lubrication of animal joints.
      or the mechanical pumping effect of unloading
      • McCutchen C.W.
      The frictional properties of animal joints.
      • Mow V.C.
      • Holmes M.H.
      • Michael Lai W.
      Fluid transport and mechanical properties of articular cartilage: a review.
      . Although finite element studies have demonstrated that migration alone can maintain interstitial fluid
      • Ateshian G.A.
      • Wang H.Q.
      A theoretical solution for the frictionless rolling-contact of cylindrical biphasic articular-cartilage layers.
      • Pawaskar S.S.
      • Jin Z.M.
      • Fisher J.
      Modelling of fluid support inside articular cartilage during sliding.
      • Accardi M.A.
      • Dini D.
      • Cann P.M.
      Experimental and numerical investigation of the behaviour of articular cartilage under shear loading-Interstitial fluid pressurisation and lubrication mechanisms.
      • Ateshian G.A.
      • Rajan V.
      • Chahine N.O.
      • Canal C.E.
      • Hung C.T.
      Modeling the matrix of articular cartilage using a continuous fiber angular distribution predicts many observed phenomena.
      , to our knowledge, the literature contains no theoretical analysis for the passive swelling hypothesis of joint recovery. There are, however, established theoretical reasons to question the feasibility of the hypothesis. First, the migrating component (e.g., femoral condyle) must not only soak enough fluid during intermittent exposure to promote its own recovery, it must more than compensate for exudation by the stationary component (e.g., tibial plateau), which is being driven by substantial fluid pressures on the order of the contact stress (1–5 MPa in most physiological conditions
      • Brand R.A.
      Joint contact stress: a reasonable surrogate for biological processes?.
      ). Second, swelling is governed by osmotic pressure, which is the product of equilibrium modulus and strain; given typical values (∼0.5 MPa, ∼10% strain
      • Eckstein F.
      • Tieschky M.
      • Faber S.
      • Englmeier K.H.
      • Reiser M.
      Functional analysis of articular cartilage deformation, recovery, and fluid flow following dynamic exercise in vivo.
      ) we would expect swelling stresses to be limited to 1–10% the competing exudation stress. Given the anatomy of a typical joint and the relative amounts of time any region spends in contact versus free-swelling, it isn't obvious that osmotic inflow should balance outflow under typical conditions. These facts suggest that passive uptake of the migrating component is unlikely to compete with exudation from the stationary component of a typical joint without assistance from another mechanism such as tribological rehydration.
      This study suggests that tribological rehydration is capable of directly rehydrating the stationary component and therefore may be a contributor to the joint recovery process in vivo. The EHD pressures that drive tribological rehydration would need to reach and potentially exceed the contact pressure. Dowson et al., for example, showed that hydrodynamic pressures in a 700 nm thick synovial fluid film can exceed 2 MPa under simulated joint conditions
      • Dowson D.
      • Jin Z.-M.
      Micro-elastohydrodynamic lubrication of synovial joints.
      . The results of this study suggest that the fluid film is substantially thinner, which implies substantially greater EHD pressures are not only possible but likely. We can conclude that the proposed driving force for tribological rehydration is competitive with that of exudation.
      As a test of the relative rates of joint and cSCA recovery, we duplicated Linn's whole joint recovery measurements
      • Linn F.C.
      Lubrication of animal joints.
      [Fig. 6(a)] as closely as possible using the cSCA configuration [Fig. 6(b)] to eliminate the possibility of free-swelling. Under dynamic conditions, Linn's ankle stabilized at and recovered to ∼100 μm of compression (two cartilage surfaces). The same basic mechanics were observed in the cSCA; the tissue compressed to ∼60 μm during sliding, thinned during static loading, and recovered during sliding at about the same rate as that observed by Linn. Although these results provide no proof of the extent to which tribological rehydration and osmotic swelling contribute to the recovery of migrating joints, they do indicate that tribological rehydration alone is capable of producing the same recovery dynamics exhibited by joints.
      Fig. 6
      Fig. 6Comparison between Linn's results
      • Mow V.C.
      • Holmes M.H.
      • Michael Lai W.
      Fluid transport and mechanical properties of articular cartilage: a review.
      and those from comparable experiments with the cSCA. The figures demonstrate striking resemblance despite grossly different loads, contact areas, reciprocation lengths, material properties, and testing configuration (whole joint versus cSCA). (a) The testing configuration of Linn used a canine ankle, which includes potential recovery contributions from free swelling during intermittent bath exposure and from tribological rehydration. (b) The cSCA configuration eliminated free swelling as a potential recovery mechanism and, therefore, effectively isolates tribological rehydration.
      The literature leaves little doubt that excessive joint space narrowing is synonymous with joint disease
      • Fife R.S.
      • Brandt K.D.
      • Braunstein E.M.
      • Katz B.P.
      • Shelburne K.D.
      • Kalasinski L.A.
      • et al.
      Relationship between arthroscopic evidence of cartilage damage and radiographic evidence of joint space narrowing in early osteoarthritis of the knee.
      • Cooper C.
      • Snow S.
      • Mcalindon T.E.
      • Kellingray S.
      • Stuart B.
      • Coggon D.
      • et al.
      Risk factors for the incidence and progression of radiographic knee osteoarthritis.
      • Hunter D.J.
      • Eckstein F.
      Exercise and osteoarthritis.
      • Leach R.E.
      • Gregg T.
      • Siber F.J.
      Weight-bearing radiography in osteoarthritis of the knee.
      . The relationship between thickness and health likely reflects the beneficial effects of: 1) interstitial hydration and pressure on lubrication, 2) fluid content on biochemistry, 3) pressure/flow on cellular stimulation and 4) fluid flow on nutrient and waste transport. Given the low modulus of cartilage and the large pressures sustained in vivo, substantial interstitial pressures must exist at all times to maintain healthy joint space. Since joints thin during inactivity, recovery during activity is the primary means by which joint space thinning is prevented in the long-term
      • Ekholm R.
      • Ingelmark B.E.
      Functional thickness variations of human articular cartilage.
      . Activity is the engine that drives and sustains important mechanical, tribological, and biological functions in the joint, which helps explain why running reduces risk of osteoarthritis
      • Williams P.T.
      Effects of running and walking on osteoarthritis and hip replacement risk.
      and why immobilization increases risk of osteoarthritis
      • Vanwanseele B.
      • Lucchinetti E.
      • Stüssi E.
      The effects of immobilization on the characteristics of articular cartilage: current concepts and future directions.
      . To date, osmotic swelling and mechanical pumping from loading and unloading are the only hypotheses we are aware of that explain this recovery phenomenon in joints. The present study 1) provides the first direct evidence of an alternate hypothesis, 2) offers a feasible conceptual framework for the relevant mechanics, 3) provides theoretical and experimental evidence that supports tribological rehydration as a significant contributor to the recovery response of natural joints, and 4) helps resolve why the literature appears to simultaneously support and refute the interstitial and fluid film theories of joint lubrication. If tribological rehydration is an important contributor to the recovery response of joints as the results suggest it is, then it must also be an important contributor to the preservation of joint health.

      Contributions

      A.C.M and D.L.B shared the discovery described, the research design, data analysis and manuscript writing.

      Competing interests

      The authors have no competing interests to disclose.

      Role of the funding source

      The research described here had no direct financial support.

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