Cartilage exhibits an extremely low friction and very low wearability within the liquid environment of the joint. It is also capable of switching wettability between superhydrophilicity and hydrophobicity in both wetting and dry conditions (specific experimental operations or open wounds). Therefore, the understanding of cartilage lubrication from the perspective of wettability provides inspiration for the design of artificial cartilage and sections with motion of soft actuators with extremely low coefficients of friction (COF). In this review, the lubrication of articular cartilage is introduced and discussed from the view of wettability. First, basic principles of articular cartilage lubrication and wettability are described with a focus on compositions and wettability of articular cartilage, and in particular the relationship between the phospholipid layers and wettability on articular cartilage, and the supramolecular synergy of synovial fluid on the lubrication of articular cartilage. Subsequently, the wettability and lubrication of articular cartilage under different stimuli (such as shear, pH, temperature, and electric field) is introduced for insights into cartilage lubrication. Finally, we present a comprehensive summary and delineate the challenges within the domain of cartilage lubrication and wettability for assisting researchers in formulating viable concepts for the design of efficient cartilage substitution or smart soft lubricating devices.

To evaluate the mechanical wear of cartilage with different types of degradation.

Bovine osteochondral explants were treated with interleukin-1β (IL-1β) to mimic inflammatory conditions, with chondroitinase ABC (ChABC) to specifically remove glycosaminoglycans (GAGs), or with collagenase to degrade the collagen network during 5 days of culture. Viscoelastic properties of cartilage were characterized via indentation. Biochemical assays were performed to quantify the cartilage matrix loss to the media during culture and from an accelerated, ex vivo wear test. The coefficient of friction during the wear test was measured. Distribution of GAGs in the tissue was assessed histologically.

All three degradative treatments decreased the cartilage modulus values and depleted GAGs in histological sections. However, wear was not uniform among the different treatments. Collagen loss from the tissue due to mechanical wear was only higher with IL-1β and collagenase treatment, while collagen loss due to wear with ChABC treatment was similar to untreated controls. In addition, less GAG was released due to mechanical wear in all degraded groups than the controls, likely because GAGs had already been depleted from these tissues during culture. As no significant differences in the coefficient of friction were observed between groups, changes in wear were attributed to altered tissue composition and structure rather than to changes in frictional forces.

Results suggest that cartilage with a degraded collagen network is more susceptible to mechanical wear, but that cartilage wear may be relatively unaffected by the loss of GAGs. Furthermore, exacerbated mechanical wear could be an additional mechanism by which inflammatory cytokines induce cartilage breakdown.

Aging, trauma, pathology, and poor natural tissue regeneration are the leading causes of osteoarthritis (OA), an articular cartilage disease. Electrospun scaffolds have gained attention as potential matrices for the treatment of OA because of their high degree of ECM mimicry, which suits chondrocyte migration, adhesion, and proliferation. However, none of the products recently introduced in the market are nanofiber-based. This study aimed to review the scope and tribology of nanofibrous articular cartilage scaffolds. Herein, we briefly discuss cartilage lubrication and strategies for promoting cell adhesion in electrospun materials. Next, we discuss the emerging need to study the biotribological properties of scaffolds. Finally, we review new perspectives on surface functionalization, surface segregation, Janus membranes, layer-by-layer fabrication, and nanofibrous composites. We conclude that cell adhesion and low-friction conciliation remain poorly explored in the recent literature. The topic intersection might create novelties in the field.

Osteoarthritis (OA) is one of the most common degenerative joint diseases, with no effective therapeutic options available. In this study, we aimed to develop an interpenetrating, in-situ-forming hydrogel based on biocompatible and anti-fouling zwitterionic (ZI) polymers for early-stage OA treatment. We hypothesized that the anti-fouling properties of zwitterions could provide tissue protection, and the high charge density of these polymers would enhance tissue penetration and lubrication. The hydrogel comprises carboxybetaine acrylamide as the ZI backbone and tyramine acrylamide as a functional comonomer to enable enzymatic and tissue-adhesive crosslinking. The hydrogel demonstrated exceptional tissue penetration and long-term retention in bovine cartilage explants. Moreover, hydrogel application protected cartilage in inflammatory media, enhanced lubrication, and decreased permeability. However, ZI hydrogel injection in collagenase-induced osteoarthritis model in rats did not prevent cartilage degeneration, and similar levels of tissue degradation and surface roughness were observed in rats injected with the ZI hydrogel and in OA controls. Additionally, ZI polymer without in-situ crosslinking resulted in increased cartilage degradation compared to both hydrogel and OA control. Furthermore, synovial tissue inflammation and significantly increased immune cell infiltration were observed in response to ZI materials. This study highlights the potential immunogenicity effect of ZI polymers in our disease model, contributing to impaired protective effects as well as exacerbated degeneration.

During daily activity, the knee joint experiences a range of complex joint motion and loading patterns. However, few studies have investigated the effects of combined motion and load to understand how interactions between these factors may affect articular hyaline cartilage at the tissue and cell level. Our objective was to quantify the effects of varying combinations of physiologically relevant analogs of specific knee movements and loading on cartilage mechanical and biological properties.

Using response surface methodology applied to an established bioreactor-indenter workflow, we quantified the effect of load (20-60N, or ∼1-3 MPa), sliding speed (1-100 mm/s) and migrating contact frequency (0.00-0.2 Hertz) on changes in cartilage stiffening ratio, cartilage deformation (i.e., surface height displacement), cell viability, histopathological score, and gene expression. All kinetic and kinematic input ranges were chosen to fall within established physiological ranges in the knee. Bioreactor testing was conducted using a ceramic counterface and a testing lubricant of culture medium.

Cartilage stiffening ratio increased after loading - the magnitude of the change was affected by load and sliding speed. Minimum cartilage deformation occurred at low load and high sliding speed. Superficial cell death was driven by an interaction of load and sliding speed, with the highest percentages of cell death at high loads. No terms were observed to have significant effects on histopathological score.

Our findings provide a better understanding of how kinematic and kinetic factors modulate cartilage responses at the matrix and the cell level, by quantifying the cartilage response using physiological input parameters.

The low friction nature of articular cartilage has been attributed to the synergistic interaction between lubricin and hyaluronic acid in the synovial fluid (SF). Lubricin is a mucinous glycoprotein that lowers the boundary mode coefficient of friction of articular cartilage in a dose-dependent manner. While there have been multiple attempts to produce recombinant lubricin and lubricin mimetic cartilage lubricants over the last two decades, these materials have not found clinical use due to challenges associated with large scale production, manufacturing, and purification. Recently, a novel method using codon scrambling was developed to produce a stable, full-length bioengineered equine lubricin (eLub) in large reproducible quantities. While preliminary frictional analysis of eLub and other recombinantly produced forms revealed they can lubricate cartilage, a complete tribological characterization is lacking, with previous studies evaluating the friction coefficient only at a single dose or a single speed. The objective of this study was to analyze the dose-dependent tribological properties of eLub using the Stribeck framework of tribological analysis. Recombinantly produced eLub at doses greater than 1.5 mg/mL exhibits friction coefficients on par with healthy bovine SF, and a maximal 5 mg/mL dose exhibits a nearly 50% lower friction coefficient than healthy SF. eLub also modulates the shift in lubrication mode of the cartilage from the high friction boundary mode to the low friction minimum mode at high concentrations.

Progressive cartilage degradation, synovial inflammation, and joint lubrication dysfunction are key markers of osteoarthritis. The composition of synovial fluid (SF) is altered in OA, with changes to both hyaluronic acid and lubricin, the primary lubricating molecules in SF. Lubricin's distinct bottlebrush mucin domain has been speculated to contribute to its lubricating ability, but the relationship between its structure and mechanical function in SF is not well understood. Here, we demonstrate the application of a novel mucinase (StcE) to selectively degrade lubricin's mucin domain in SF to measure its impact on joint lubrication and friction. Notably, StcE effectively degraded the lubricating ability of SF in a dose-dependent manner starting at nanogram concentrations (1-3.2 ng/mL). Further, the highest StcE doses effectively degraded lubrication to levels on par with trypsin, suggesting that cleavage at the mucin domain of lubricin is sufficient to completely inhibit the lubrication mechanism of the collective protein component in SF. These findings demonstrate the value of mucin-specific experimental approaches to characterize the lubricating properties of SF and reveal key trends in joint lubrication that help us better understand cartilage function in lubrication-deficient joints.

Articular joints facilitate motion and transfer loads to underlying bone through a combination of cartilage tissue and synovial fluid, which together generate a low-friction contact surface. Traumatic injury delivered to cartilage and the surrounding joint capsule causes secretion of proinflammatory cytokines by chondrocytes and the synovium, triggering cartilage matrix breakdown and impairing the ability of synovial fluid to lubricate the joint. Once these inflammatory processes become chronic, posttraumatic osteoarthritis (PTOA) development begins. However, the exact mechanism by which negative alterations to synovial fluid leads to PTOA pathogenesis is not fully understood. We hypothesize that removing the lubricating macromolecules from synovial fluid alters the relationship between mechanical loads and subsequent chondrocyte behavior in injured cartilage. To test this hypothesis, we utilized an ex vivo model of PTOA that involves subjecting cartilage explants to a single rapid impact followed by continuous articulation within a lubricating bath of either healthy synovial fluid, phosphate-buffered saline (PBS), synovial fluid treated with hyaluronidase, or synovial fluid treated with trypsin. These treatments degrade the main macromolecules attributed with providing synovial fluid with its lubricating properties; hyaluronic acid and lubricin. Explants were then bisected and fluorescently stained to assess global and depth-dependent cell death, caspase activity, and mitochondrial depolarization. Explants were tested via confocal elastography to determine the local shear strain profile generated in each lubricant. These results show that degrading hyaluronic acid or lubricin in synovial fluid significantly increases middle zone chondrocyte damage and shear strain loading magnitudes, while also altering chondrocyte sensitivity to loading.

Healthy articular cartilage is a remarkable bearing material optimized for near-frictionless joint articulation. Because its limited self-repair capacity renders it susceptible to osteoarthritis (OA), approaches to reinforce or rebuild degenerative cartilage are of significant interest. While exogenous collagen crosslinking (CXL) treatments improve cartilage's mechanical properties and increase its resistance to enzymatic degradation, their effects on cartilage lubrication remain less clear. Here, we examined how the collagen crosslinking agents genipin (GP) and glutaraldehyde (GTA) impact cartilage lubrication using the convergent stationary contact area (cSCA) configuration. Unlike classical configurations, the cSCA sustains biofidelic kinetic friction coefficients (μk) via superposition of interstitial and hydrodynamic pressurization (i.e., tribological rehydration). As expected, glutaraldehyde- and genipin-mediated CXL increased cartilage's tensile and compressive moduli. Although net tribological rehydration was retained after CXL, GP or GTA treatment drastically elevated μk. Both healthy and "OA-like" cartilage (generated via enzymatic digestion) sustained remarkably low μk in saline- (≤0.02) and synovial fluid-lubricated contacts (≤0.006). After CXL, μk increased up to 30-fold, reaching values associated with marked chondrocyte death in vitro. These results demonstrate that mechanical properties (i.e., stiffness) are necessary, but not sufficient, metrics of cartilage function. Furthermore, the marked impairment in lubrication suggests that CXL-mediated stiffening is ill-suited to cartilage preservation or joint resurfacing.

Cartilage degeneration is a characteristic of osteoarthritis (OA), which is often observed in aging populations. This degeneration is due to the breakdown of articular cartilage (AC) mechanical and tribological properties primarily attributed to lubrication failure. Understanding the reasons behind these failures and identifying potential solutions could have significant economic and societal implications, ultimately enhancing quality of life. This review provides an overview of developments in the field of AC, focusing on its mechanical and tribological properties. The emphasis is on the role of lubrication in degraded AC, offering insights into its structure and function relationship. Further, it explores the fundamental connection between AC mechano-tribological properties and the advancement of its degradation and puts forth recommendations for strategies to boost its lubrication efficiency.

Restoration of the lubrication functions of articular cartilage is an effective treatment to alleviate the progression of osteoarthritis (OA). Herein, we fabricated chitosan-block-poly(sulfobetaine methacrylate) (CS-b-pSBMA) copolymer via a free radical polymerization of sulfobetaine methacrylate onto activated chitosan segment, structurally mimicking the lubricating biomolecules on cartilage. The successful copolymerization of CS-b-pSBMA was verified by Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and 1H nuclear magnetic resonance. Friction test confirmed that the CS-b-pSBMA copolymer could achieve an excellent lubrication effect on artificial joint materials such as Ti6Al4V alloy with a coefficient of friction as low as 0.008, and on OA-simulated cartilage, better than the conventional lubricant hyaluronic acid, and the adsorption effect of lubricant on cartilage surface was proved by a fluorescence labeling experiment. In addition, CS-b-pSBMA lubricant possessed an outstanding stability, which can withstand enzymatic degradation and even a long-term storage up to 4 weeks. In vitro studies showed that CS-b-pSBMA lubricant had a favorable antibacterial activity and good biocompatibility. In vivo studies confirmed that the CS-b-pSBMA lubricant was stable and could alleviate the degradation process of cartilage in OA mice. This biomimetic lubricant is a promising articular joint lubricant for the treatment of OA and cartilage restoration.

Articular cartilage's remarkable low-friction properties are essential to joint function. In osteoarthritis (OA), cartilage degeneration (e.g., proteoglycan loss and collagen damage) decreases tissue modulus and increases permeability. Although these changes impair lubrication in fully depressurized and slowly slid cartilage, new evidence suggests such relationships may not hold under biofidelic sliding conditions more representative of those encountered in vivo. Our recent studies using the convergent stationary contact area (cSCA) configuration demonstrate that articulation (i.e., sliding) generates interfacial hydrodynamic pressures capable of replenishing cartilage interstitial fluid/pressure lost to compressive loading through a mechanism termed tribological rehydration. This fluid recovery sustains in vivo-like kinetic friction coefficients (µk<0.02 in PBS and <0.005 in synovial fluid) with little sensitivity to mechanical properties in healthy tissue. However, the tribomechanical function of compromised cartilage under biofidelic sliding conditions remains unknown. Here, we investigated the effects of OA-like changes in cartilage mechanical properties, modeled via enzymatic digestion of mature bovine cartilage, on its tribomechanical function during cSCA sliding. We found no differences in sliding-driven tribological rehydration behaviors or µk between naïve and digested cSCA cartilage (in PBS or synovial fluid). This suggests that OA-like cartilage retains sufficient functional properties to support naïve-like fluid recovery and lubrication under biofidelic sliding conditions. However, OA-like cartilage accumulated greater total tissue strains due to elevated strain accrual during initial load application. Together, these results suggest that elevated total tissue strains-as opposed to activity-mediated strains or friction-driven wear-might be the key biomechanical mediator of OA pathology in cartilage. STATEMENT OF SIGNIFICANCE: Osteoarthritis (OA) decreases cartilage's modulus and increases its permeability. While these changes compromise frictional performance in benchtop testing under low fluid load support (FLS) conditions, whether such observations hold under sliding conditions that better represent the joints' dynamic FLS conditions in vivo is unclear. Here, we leveraged biofidelic benchtop sliding experiments-that is, those mimicking joints' native sliding environment-to examine how OA-like changes in mechanical properties effect cartilage's natural lubrication. We found no differences in sliding-mediated fluid recovery or kinetic friction behaviors between naïve and OA-like cartilage. However, OA-like cartilage experienced greater strain accumulation during load application, suggesting that elevated tissue strains (not friction-driven wear) may be the primary biomechanical mediator of OA pathology.

Healthy articular cartilage exhibits remarkable resistance to wear, sustaining mechanical loads and relative motion for decades. However, tissues that replace or repair cartilage defects are much less long lasting. Better information on the compositional and material characteristics that contribute to the wear resistance of healthy cartilage could help guide strategies to replace and repair degenerated tissue. The main objective of this study was to assess the relationship between wear of healthy articular cartilage, its biochemical composition, and its viscoelastic material properties. The correlation of these factors with the coefficient of friction during the wear test was also evaluated. Viscoelastic properties of healthy bovine cartilage were determined via stress relaxation indentation. The same specimens underwent an accelerated, in vitro wear test, and the amount of glycosaminoglycans (GAGs) and collagen released during the wear test were considered measures of wear. The frictional response during the wear test was also recorded. The GAG, collagen and water content and the concentration of the enzymatic collagen crosslink pyridinoline were quantified in tissue that was adjacent to each wear test specimen. Finally, correlation analysis was performed to identify potential relationships between wear characteristics of healthy articular cartilage with its composition, viscoelastic material properties and friction. The findings suggest that stiffer cartilage with higher GAG, collagen and water content has a higher wear resistance. Enzymatic collagen crosslinks also enhance the wear resistance of the collagen network. The parameters of wear, composition, and mechanical stiffness of cartilage were all correlated with one another, suggesting that they are interrelated. However, friction was largely independent of these in this study. The results identify characteristics of healthy articular cartilage that contribute to its remarkable wear resistance. These data may be useful for guiding techniques to restore, regenerate, and stabilize cartilage tissue.

Intra-articular injections of hyaluronic acid have been a mainstay of osteoarthritis treatment for decades. However, controversy surrounds the mechanism of action and efficacy of this therapy. As such, there has been recent interest in developing synthetic lubricants that lubricate cartilage. Recently, a synthetic 4 wt% polyacrylamide (pAAm) hydrogel was shown to effectively decrease lameness in horses. However, its mechanism of action and ability to lubricate cartilage is unknown. The goal of this study was to characterize the lubricating ability of this hydrogel and determine its efficacy for healthy and degraded cartilage. The study utilized previously established IL-1β-induced biochemical degradation and mechanical impact injury models to degrade cartilage. The lubricating ability of the hydrogel was then characterized using a custom-built tribometer using a glass counterface and friction was evaluated using the Stribeck framework for articular cartilage. pAAm hydrogel was shown to significantly lower the friction coefficient of cartilage explants from both degradation models (30%-40% reduction in friction relative to controls). A striking finding from this study was the aggregation of the pAAm hydrogel at the articulating surface. The surface aggregation was observed in the histological sections of explants from all treatment groups after tribological evaluation. Using the Stribeck framework, the hydrogel was mapped to higher Sommerfeld numbers and was characterized as a viscous lubricant predominantly in the minimum friction mode. In summary, this study revealed that pAAm hydrogel lubricates native and degraded cartilage explants effectively and may have an affinity for the articulating surface of the cartilage.

Due to its high molecular weight and viscosity, hyaluronic acid (HA) is widely used for viscosupplementation to provide joint pain relief in osteoarthritis. However, this benefit is temporary due to poor adhesion of HA on articular surfaces. In this study, we therefore conjugated HA with dopamine to form HADN, which made the HA adhesive while retaining its viscosity enhancement capacity. We hypothesized that HADN could enhance cartilage lubrication through adsorption onto the exposed collagen type II network and repair the lamina splendens. HADN was synthesized by carbodiimide chemistry between hyaluronic acid and dopamine. Analysis of Magnetic Resonance (NMR) and Ultraviolet spectrophotometry (Uv-vis) showed that HADN was successfully synthesized. Adsorption of HADN on collagen was demonstrated using Quartz crystal microbalance with dissipation (QCM-D). Ex vivo tribological tests including measurement of coefficient of friction (COF), dynamic creep, in stance (40 N) and swing (4 N) phases of gait cycle indicated adequate protection of cartilage by HADN with higher lubrication compared to HA alone. HADN solution at the cartilage-glass sliding interface not only retains the same viscosity as HA and provides fluid film lubrication, but also ensures better boundary lubrication through adsorption. To confirm the cartilage surface protection of HADN, we visualized cartilage wear using optical coherence tomography (OCT) and atomic force microscopy (AFM).

Healthy articular cartilage supports load bearing and frictional properties unmatched among biological tissues and man-made bearing materials. Balancing fluid exudation and recovery under loaded and articulated conditions is essential to the tissue's biological and mechanical longevity. Our prior tribological investigations, which leveraged the convergent stationary contact area (cSCA) configuration, revealed that sliding alone can modulate cartilage interstitial fluid pressurization and the recovery and maintenance of lubrication under load through a mechanism termed 'tribological rehydration.' Our recent comparative assessment of tribological rehydration revealed remarkably consistent sliding speed-dependent fluid recovery and lubrication behaviors across femoral condyle cartilage from five mammalian species (equine/horse, bovine/cow, porcine/pig, ovine/sheep, and caprine/goat). In the present study, we identified and characterized key predictive relationships among tissue properties, sliding-induced tribological rehydration, and the modulation/recovery of lubrication within healthy articular cartilage. Using correlational analysis, we linked observed speed-dependent tribological rehydration behaviors to cartilage's geometry and biphasic properties (tensile and compressive moduli, and permeability). Together, these findings demonstrate that easily measurable biphasic tissue characteristics (e.g., bulk tissue material properties, compressive strain magnitude, and strain rates) can be used to predict cartilage's rehydration and lubricating abilities, and ultimately its function in vivo. STATEMENT OF SIGNIFICANCE: In healthy cartilage, articulation recovers fluid lost to static loading thereby sustaining tissue lubricity. Osteoarthritis causes changes to cartilage composition, stiffness, and permeability associated with faster fluid exudation and presumably poorer frictional outcomes. Yet, the relationship between mechanical properties and fluid recovery during articulation/sliding remains unclear. Through innovative, high-speed benchtop sliding and indentation experiments, we found that cartilage's tissue properties regulate its exudation/hydration under slow sliding speeds but have minimal effect at high sliding speeds. In fact, cartilage rehydration appears insensitive to permeability and stiffness under high fluid load support conditions. This new understanding of the balance of cartilage exudation and rehydration during activity, based upon comparative tribology studies, may improve prevention and rehabilitation strategies for joint injuries and osteoarthritis.

The purpose of this study was to investigate the feasibility of adipose-derived stem cells (ADSCs) as the seed cells of cartilage tissue engineering. ADSCs were isolated from adipose tissue that was harvested under sterile conditions from the inguen fold of porcines and cultured in vitro. Acellular cartilage extracellular matrix (ACECM) scaffolds of pigs were then constructed. Moreover, inflammatory cells, as well as cellular and humoral immune responses, were detected using hematoxylin and eosin staining staining, immunohistochemical staining, and western blot analysis. The results showed that the cartilage complex constructed by ADSCs and ACECM through tissue engineering successfully repaired the cartilage defect of the pig knee joint. The in vivo repair experiment showed no significant difference between chondrocytes, ADSCs, and induced ADSCs, indicating that ADSCs do not require in vitro induction and have the potential for chondrogenic differentiation in the environment around the knee joint. In addition, pig-derived acellular cartilage scaffolds possess no obvious immune inflammatory response when used in xenotransplantation. ADSCs may serve as viable seed cells for cartilage tissue engineering.

Inferior synovial lubrication is a hallmark of osteoarthritis (OA), and synovial fluid (SF) lubrication and composition are variable among OA patients. Hyaluronic acid (HA) viscosupplementation is a widely used therapy for improving SF viscoelasticity and lubrication, but it is unclear how the effectiveness of HA viscosupplements varies with arthritic endotype. The objective of this study was to investigate the effects of the HA viscosupplement, Hymovis®, on the lubricating properties of diseased SF from patients with noninflammatory OA and inflammatory arthritis (IA). The composition (cytokine, HA, and lubricin concentrations) of the SF was measured as well as the mechanical properties (rheology, tribology) of the SF alone and in a 1:1 mixture with the HA viscosupplement. Using rotational rheometry, no difference in SF viscosity was detected between disease types, and the addition of HA significantly increased all fluids' viscosities. In noninflammatory OA SF, friction coefficients followed a typical Stribeck pattern, and their magnitude was decreased by the addition of HA. While some of the IA SF also showed typical Stribeck behavior, a subset showed more erratic behavior with highly variable and larger friction coefficients. Interestingly, this aberrant behavior was not eliminated by the addition of HA, and it was associated with low concentrations of lubricin. Aberrant SF exhibited significantly lower effective viscosities compared to noninflammatory OA and IA SF with typical tribological behavior. Collectively, these results suggest that different endotypes of arthritis exist with respect to lubrication, which may impact the effectiveness of HA viscosupplements in reducing friction.

To compare the efficacy of mesenchymal stem cell (MSC) exosomes with hyaluronic acid (HA) against HA alone for functional cartilage regeneration in a rabbit osteochondral defect model.

Critical-size osteochondral defects (4.5-mm diameter and 1.5-mm depth) were created on the trochlear grooves in the knees of 18 rabbits and were randomly allocated to 2 treatment groups: (1) exosomes and HA combination and (2) HA alone. Three 1-mL injections of either exosomes and HA or HA alone were administered intra-articularly immediately after surgery and thereafter at 7 and 14 days after surgery. At 6 and 12 weeks, gross evaluation, histologic and immunohistochemical analysis, and scoring were performed. The functional biomechanical competence of the repaired cartilage also was evaluated.

Compared with defects treated with HA, defects treated with exosomes and HA showed significant improvements in macroscopic scores (P = .032; P = .001) and histologic scores (P = .005; P < .001) at 6 and 12 weeks, respectively. Defects treated with exosomes and HA also demonstrated improvements in mechanical properties compared with HA-treated defects, with significantly greater Young's moduli (P < .05) and stiffness (P < .05) at 6 and 12 weeks. By 12 weeks, the newly-repaired tissues in defects treated with exosomes and HA composed mainly of hyaline cartilage that are mechanically and structurally superior to that of HA-treated defects and demonstrated mechanical properties that approximated that of adjacent native cartilage (P > .05). In contrast, HA-treated defects showed some repair at 6 weeks, but this was not sustained, as evidenced by significant deterioration of histologic scores (P = .002) and a plateau in mechanical properties from 6 to 12 weeks.

This study shows that the combination of MSC exosomes and HA administered at a clinically acceptable frequency of 3 intra-articular injections can promote sustained and functional cartilage repair in a rabbit post-traumatic cartilage defect model, when compared with HA alone.

Human MSC exosomes and HA administered in combination promote functional cartilage repair and may represent a promising cell-free therapy for cartilage repair in patients.

To examine coefficients of friction (COFs) of articular cartilage, it is necessary to use cartilage as a friction partner. Irregularities of surfaces require special tribometers and calculation methods. The aim of this study was to establish a tribometer system for measuring a low COF of cartilage and to develop and validate an algorithm that takes the irregularities into consideration. We used a pin-on-plate tribometer that allows a vertical displacement of the pin to follow the surface of the plate and developed an algorithm that takes these irregularities into account. We were, thus, able to take into consideration a forward and backward movement, an upward and downward movement, and different force ratios. The algorithm was validated using a spherical POM (polyoxymethylene) pin against a stainless steel plate at slope angles up to 24°. First examinations with articular cartilage against articular cartilage samples of a stifle joint of a pig were then performed. The newly developed tribometer worked well when POM against a stainless steel hump was examined. The COF increased for slope angles steeper than ±15°. There was an interaction between the COF and the slope angle, but not for the range within ±15°. Cartilage examinations revealed COFs as published in the literature. The tribometer and the algorithm were suitable for the detection of low COF of irregular surfaces of the plate within a range of ±15°. The COF resulting from the forward and backward movements should be averaged.

A poly(7-oxanorbornene-2-carboxylate) polymer containing pendent triethyleneglycol (TEG) chains of 2.8 MDa ("2.8M TEG") was synthesized and evaluated for long-term lubrication and wear reduction of ex vivo bovine cartilage as well as for synovitis in rats and dogs after intra-articular administration. Bovine cartilage surfaces were tested under torsional friction for 10,080 rotations while immersed in either saline, bovine synovial fluid (BSF), or 2.8M TEG. For each solution, coefficient of friction (μ), changes in surface roughness, and lost cartilage glycosaminoglycan were compared. To directly compare 2.8M TEG and BSF, additional samples were tested sequentially in BSF, BSF, 2.8M TEG, and then BSF. Finally, another set of samples were tested twice in saline to induce surface roughness and then tested in BSF, Synvisc, or 2.8M TEG to determine each treatment's effect on worn cartilage. Next, male Lewis rats were injected in one knee with 2.8M TEG or saline and evaluated for effects on gait, and female beagles were injected with either 2.8M TEG or saline in one knee, and their synovial tissues analyzed for inflammation by H&E staining. Treatment with 2.8M TEG lowers μ, lessens surface roughness, and minimizes glycosaminoglycan loss compared to saline. The 2.8M TEG also reduces μ compared to BSF in pairwise testing and on worn cartilage surfaces. Injection of 2.8M TEG in rat or beagle knees gives comparable effects to treatment with saline, and does not cause significant synovitis.

Hyaluronic acid injections have been a mainstay of arthritis treatment for decades. However, much controversy remains about their clinical efficacy and their potential mechanism of action. This approach to arthritis therapy is often called viscosupplementation, a term which is rooted in the elevated viscosity of the injected solutions. This terminology also suggests a mechanical pathway of action and further implies that their efficacy is dependent on viscosity. Notably, previous studies of the relationship between viscous properties of hyaluronic acid solutions and their clinical efficacy have not been definitive. Recently we developed an experimental and analytical framework for studying cartilage lubrication that captures the Stribeck-like behavior of cartilage in an elastoviscous transition curve. Here we apply this framework to study the lubricating behavior of six hyaluronan products currently used for injectable arthritis therapy in the US. Despite the fact that the source and chemical modifications endow these products with a range of lubricating properties, we show that the lubricating effect of all of these materials can be described by this Stribeck-like elastoviscous transition. Fitting this data to the elastoviscous transition model enables the calculation of effective lubricating viscosities for each material, which differ substantially from the viscosities measured using standard rheometry. Further we show that while data from standard rheometry are poor predictors of clinical performance of these materials, measurements of friction coefficient and effective lubricating viscosity correlate well (R2 = 0.77; p < 0.005) with assessments of improved clinical function reported previously. This approach offers both a novel method that can be used to evaluate potential clinical efficacy of hyaluronic acid formulations and provide new insight on their mode of action.

The objective of this study was to examine temporal variations in synovial fluid composition and lubrication following articular fracture. Post-traumatic osteoarthritis (PTOA) was induced by creating an osteochondral fracture in the middle carpal joint of four horses while the contralateral limb served as a sham-operated control. Horses were exercised on a high-speed treadmill, and synovial fluid was collected pre-operatively and at serial timepoints until 75 days post-operatively. Lubricin and hyaluronic acid (HA) concentrations were measured using sandwich ELISAs, and the molecular weight distribution of HA was analyzed via gel electrophoresis. Synovial fluid viscosity and cartilage friction coefficients across all modes of lubrication were measured on days 0, 19, 33, and 61 using a commercial rheometer and a custom tribometer, respectively. HA concentrations were significantly decreased post-operatively, and high molecular weight HA (>6.1MDa) did not recover to pre-operative values by the study termination at day 75. Lubricin concentrations increased after surgery to a greater extent in the OA as compared to sham-operated limbs. Viscosity was significantly reduced after surgery. While boundary and elastoviscous mode friction coefficients did not vary, the transition number, representing the shift between these modes, was lower. Although more pronounced in the OA limbs, similar derangements in HA, HA molecular weight distribution, viscosity, and transition number were observed in the sham-operated limbs, which may be explained by synovial fluid washout during arthroscopy. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.