Load sharing between solid and fluid phases in articular cartilage: II--Comparison of experimental results and u-p finite element predictions.

Experimental measurements in conjunction with theoretical predictions were used to determine the extent of load supported by the fluid phase of cartilage at the articular surface. The u-p finite element model was used to simulate the loading of six separate porcine knee joints and to predict surface deformations of the cartilage layer on the lateral femoral condyle. Representative geometry for the condyle, contact pressures, and intrinsic material properties of the cartilage layer were supplied from experimental measures (see Part I). The u-p finite element predictions for surface deformations of the cartilage layer were obtained for several load partitioning states between the solid and fluid phases of cartilage at the articular surface. These were then compared to actual surface deformations obtained experimentally. It appeared from the comparison that approximately 75 percent of the applied load was borne by the fluid phase at the articular surface under this loading regime. This was qualitatively in agreement with the hypothesis that an applied load to articular joints is partitioned at the surface to the two phases according to the surface area ratios of the solid and fluid phases. It appeared that the solid phase was shielded from the total applied stress on the articular surface by the fluid and could be a reason for the excellent durability of the tissue under the demanding conditions in a diarthrodial joint.     

Distinct horizontal patterns in the spatial organization of superficial zone chondrocytes of human joints

A better understanding of the unique cellular and functional properties of the superficial zone of articular cartilage may aid current strategies in tissue engineering which attempts a layered design for the repair of cartilage lesions to avert or postpone the onset of osteoarthritis. However, data pertaining to the cellular organization of non-degenerated superficial zone of articular cartilage is not available for most human joints. The present study analyzed the arrangement of chondrocytes of non-degenerated human joints (shoulder, elbow, knee, and ankle) by using fluorescence microscopy of the superficial zone in a top-down view. The resulting horizontal chondrocyte arrangements were tested for randomness, homogeneity or a significant grouping via point pattern analysis and were correlated with the joint type in which they occurred. The present study demonstrated that human superficial chondrocytes occurred in four distinct patterns of strings, clusters, pairs or single chondrocytes. Those patterns represented a significant grouping (p < 0.0001) with horizontal alignment. Each articular joint surface was dominated by only one of these four patterns (p < 0.001). Specific patterns correlated with specific diarthrodial joint types (p < 0.001). Further studies need to establish whether these organizational patterns are a consequence of their surrounding environment or whether they are linked to a functional purpose.     

Congruency effects on load bearing in diarthrodial joints

Modelling load bearing in diarthrodial joints is challenging, due to the complexity of the materials, the boundary and interface conditions and the geometry. The articulating surfaces are covered with cartilage layers that are filled with a fluid that plays a major role in load bearing [Mow, V.C., Holmes, M.H., Lai, W.M. (1984) "Survey article: fluid transport and mechanical properties of articular cartilage: a review", Journal of Biomechanics 17(5), 377-394]. Researchers have tended to approximate joint geometry using axisymmetry [Donzelli, P.S., Spilker, R.L., Ateshian, G.A., Mow, V.C. (1999) "Contact analysis of biphasic transversely isotropic cartilage layers and correlations with tissue failure", Journal of Biomechanics 32, 1037-1047], often with a rounded upper articulating surface, creating a form of Hertz problem [Donzelli, P.S., Spilker, R.L., Ateshian, G.A., Mow, V.C. (1999) "Contact analysis of biphasic transversely isotropic cartilage layers and correlations with tissue failure", Journal of Biomechanics 32, 1037-1047]. However, diarthrodial joints (shoulder, hip and knee) are equipped with peripheral structures (glenoid labrum, acetabular labrum and meniscus, respectively) that tend to deepen the joint contact and thus cause initial contact to be established at the periphery of the joint rather than "centrally". The surface geometries are purposefully incongruent, and the incongruency has a significant effect on the stresses, pressures and pressure gradients inside the tissue. The models show the importance of the peripheral structures and the incongruency from a load-bearing perspective. Joint shapes must provide a compromise between demands for load-bearing, lubrication and the supply of nutrients to the chondrocytes of the cartilage and cells of the peripheral structures. Retention and repair of the functionality of these peripheral structures should be a prime consideration in any surgical treatment of an injured joint.     

Congruency Effects on Load Bearing in Diarthrodial Joints

Modelling load bearing in diarthrodial joints is challenging, due to the complexity of the materials, the boundary and interface conditions and the geometry. The articulating surfaces are covered with cartilage layers that are filled with a fluid that plays a major role in load bearing [Mow, V.C., Holmes, M.H., Lai, W.M. (1984) “Survey article: fluid transport and mechanical properties of articular cartilage: a review”, Journal of Biomechanics 17(5), 377–394]. Researchers have tended to approximate joint geometry using axisymmetry [Donzelli, P.S., Spilker, R.L., Ateshian, G.A., Mow, V.C. (1999) “Contact analysis of biphasic transversely isotropic cartilage layers and correlations with tissue failure”, Journal of Biomechanics 32, 1037–1047], often with a rounded upper articulating surface, creating a form of Hertz problem [Donzelli, P.S., Spilker, R.L., Ateshian, G.A., Mow, V.C. (1999) “Contact analysis of biphasic transversely isotropic cartilage layers and correlations with tissue failure”, Journal of Biomechanics 32, 1037–1047]. However, diarthrodial joints (shoulder, hip and knee) are equipped with peripheral structures (glenoid labrum, acetabular labrum and meniscus, respectively) that tend to deepen the joint contact and thus cause initial contact to be established at the periphery of the joint rather than “centrally”. The surface geometries are purposefully incongruent, and the incongruency has a significant effect on the stresses, pressures and pressure gradients inside the tissue. The models show the importance of the peripheral structures and the incongruency from a load-bearing perspective. Joint shapes must provide a compromise between demands for load-bearing, lubrication and the supply of nutrients to the chondrocytes of the cartilage and cells of the peripheral structures. Retention and repair of the functionality of these peripheral structures should be a prime consideration in any surgical treatment of an injured joint.     

Effects of inserting a pressensor film into articular joints on the actual contact mechanics.

Fuji film has been widely used in studies aimed at obtaining the contact mechanics of articular joints. Once sealed for practical use in biological joints, Fuji Pressensor film has a total effective thickness of 0.30 mm, which is comparable to the cartilage thickness in the joints of many small animals. The average effective elastic modulus of Fuji film is approximately 100 MPa in compression, which is larger by a factor of 100-300 compared to that of normal articular cartilage. Therefore, inserting a Pressensor film into an articular joint will change the contact mechanics of the joint. The measurement precision of the Pressensor film has been determined systematically; however, the changes in contact mechanics associated with inserting the film into joints have not been investigated. This study was aimed at quantifying the changes in the contact mechanics associated with inserting sealed Fuji Pressensor film into joints. Spherical and cylindrical articular joint contact mechanics with and without Pressensor film and for varying degrees of surface congruency were analyzed and compared by using finite element models. The Pressensor film was taken as linearly elastic and the cartilage was assumed to be biphasic, composed of a linear elastic solid phase and an inviscid fluid phase. The present analyses showed that measurements of the joint contact pressures with Fuji Pressensor film will change the maximum true contact pressures by 10-26 percent depending on the loading, geometry of the joints, and the mechanical properties of cartilage. Considering this effect plus the measurement precision of the film (approximately 10 percent), the measured joint contact pressures in a joint may contain errors as large as 14-28 percent.     

A surface roughness comparison of cartilage in different types of synovial joints

The naturally occurring structure of articular cartilage has proven to be an effective means for the facilitation of motion and load support in equine and other animal joints. For this reason, cartilage has been extensively studied for many years. Although the roughness of cartilage has been determined from atomic force microscopy (AFM) and other methods in multiple studies, a comparison of roughness to joint function has not be completed. It is hypothesized that various joint types with different motions and regimes of lubrication have altered demands on the articular surface that may affect cartilage surface properties. Micro- and nanoscale stylus profilometry was performed on the carpal cartilage harvested from 16 equine forelimbs. Eighty cartilage surface samples taken from three different functioning joint types (radiocarpal, midcarpal, and carpometacarpal) were measured by a Veeco Dektak 150 Stylus Surface Profilometer. The average surface roughness measurements were statistically different for each joint. This indicates that the structure of cartilage is adapted to, or worn by, its operating environment. Knowledge of cartilage micro- and nanoscale roughness will assist the future development and design of treatments for intra- articular substances or surfaces to preserve joint integrity and reduce limitations or loss of joint performance.     

In Vivo Dynamic Deformation of Articular Cartilage in Intact Joints Loaded by Controlled Muscular Contractions

When synovial joints are loaded, the articular cartilage and the cells residing in it deform. Cartilage deformation has been related to structural tissue damage, and cell deformation has been associated with cell signalling and corresponding anabolic and catabolic responses. Despite the acknowledged importance of cartilage and cell deformation, there are no dynamic data on these measures from joints of live animals using muscular load application. Research in this area has typically been done using confined and unconfined loading configurations and indentation testing. These loading conditions can be well controlled and allow for accurate measurements of cartilage and cell deformations, but they have little to do with the contact mechanics occurring in a joint where non-congruent cartilage surfaces with different material and functional properties are pressed against each other by muscular forces. The aim of this study was to measure in vivo, real time articular cartilage deformations for precisely controlled static and dynamic muscular loading conditions in the knees of mice. Fifty and 80% of the maximal knee extensor muscular force (equivalent to approximately 0.4N and 0.6N) produced average peak articular cartilage strains of 10.5±1.0% and 18.3±1.3% (Mean ± SD), respectively, during 8s contractions. A sequence of 15 repeat, isometric muscular contractions (0.5s on, 3.5s off) of 50% and 80% of maximal muscular force produced cartilage strains of 3.0±1.1% and 9.6±1.5% (Mean ± SD) on the femoral condyles of the mouse knee. Cartilage thickness recovery following mechanical compression was highly viscoelastic and took almost 50s following force removal in the static tests.     

Structural and functional changes of the articular surface in a post-traumatic model of early osteoarthritis measured by atomic force microscopy

The functional integrity of the articulating cartilage surface is a critical determinant of joint health. Although a variety of techniques exist to characterize the structural changes in the tissue with osteoarthritis (OA), some with extremely high resolution, most lack the ability to detect and monitor the functional changes that accompany the structural deterioration of this essential bearing surface. Atomic force microscopy (AFM) enables the acquisition of both structural and mechanical properties of the articular cartilage surface, with up to nanoscale resolution, making it particularly useful for evaluating the functional behavior of the macromolecular network forming the cartilage surface, which disintegrates in OA.In the present study, AFM was applied to the articular cartilage surfaces from six pairs of canine knee joints with post-traumatic OA. Microstructure (RMS roughness) and micromechanics (dynamic indentation modulus, E^?) of medial femoral condyle cartilages were compared between contralateral controls and cruciate-transected knee joints, which develop early signs of OA by three months after surgery.Results reveal a significant increase in RMS roughness and a significant four-fold decrease in E^? in cartilages from cruciate-transected joints versus contralateral controls. Compared to previous reports of changes in bulk mechanics, AFM was considerably more sensitive at detecting early cartilage changes due to cruciate-deficiency. The use of AFM in this study provides important new information on early changes in the natural history of OA because of its ability to sensitively detect and measure local structural and functional changes of the articular cartilage surface, the presumptive site of osteoarthritic initiation.     

Material and functional properties of articular cartilage and patellofemoral contact mechanics in an experimental model of osteoarthritis

The purposes of this study were to determine the in situ functional and material properties of articular cartilage in an experimental model of joint injury, and to quantify the corresponding in situ joint contact mechanics. Experiments were performed in the anterior cruciate ligament (ACL) transected knee of the cat and the corresponding, intact contralateral knee, 16 weeks following intervention. Cartilage thickness, stiffness, effective Young’s modulus, and permeability were measured and derived from six locations of the knee. The total contact area and peak pressures in the patellofemoral joint were obtained in situ using Fuji Pressensor film, and comparisons between experimental and contralateral joint were made for corresponding loading conditions. Total joint contact area and peak pressure were increased and decreased significantly (=0.01), respectively, in the experimental compared to the contralateral joint. Articular cartilage thickness and stiffness were increased and decreased significantly (=0.01), respectively, in the experimental compared to the contralateral joint in the four femoral and patellar test locations. Articular cartilage material properties (effective Young’s modulus and permeability) were the same in the ACL-transected and intact joints. These results demonstrate for the first time the effect of changes in articular cartilage properties on the load transmission across a joint. They further demonstrate a substantial change in the joint contact mechanics within 16 weeks of ACL transection. The results were corroborated by theoretical analysis of the contact mechanics in the intact and ACL-transected knee using biphasic contact analysis and direct input of cartilage properties and joint surface geometry from the experimental animals. We conclude that the joint contact mechanics in the ACL-transected cat change within 16 weeks of experimental intervention.     

Lubricin: a novel potential biotherapeutic approaches for the treatment of osteoarthritis

Osteoarthritis (OA) is a multi-factor disorder of sinovial joints, which characterized by escalated degeneration and loss of articular cartilage. Treatment of OA is a critical unmet need in medicine for regeneration of damaged articular cartilage in elderly. On the other hand, lubricin, a glycoprotein specifically synthesized by chondrocytes located at the surface of articular cartilage, has been shown to provide boundary lubrication of congruent articular surfaces under conditions of high contact pressure and near zero sliding speed. Lubrication of these surfaces is critical to normal joint function, while different gene expressions of lubricin had been found in the synovium of rheumatoid arthritis (RA) and OA. Moreover, mutations or lacking of lubricin gene have been shown to link to the joint disease such as camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP), synovial hyperplasia and failure of joint function, suggesting an important role of lubricin in the pathogenesis of these joint disease. Recent studies demonstrate that administration with recombinant lubricin in the joint cavity would be effective in the prevention of cartilage degeneration in animal OA models. Therefore, a treatment with lubricin which would protect cartilage in vivo would be desirable. This article reviews recent findings with regard to the possible role of lubricin in the progression of OA, and further discusses lubricin as a novel potential biotherapeutic approaches for the treatment of OA.     

A comparison of the influence of global functional loads vs. local contact anatomy on articular cartilage thickness at the knee

Cartilage contact geometry, along with joint loading, can play an important role in determining local articular cartilage tissue stress. Thus individual variations in cartilage thickness can be associated with both individual variations in joint loading associated with activities of daily living as well as individual differences in the anatomy of the contacting surfaces of the joint. The purpose of this study was to isolate the relationship between cartilage thickness predicted by individual variations in contact surface geometry based on the radii of the femur and tibia vs. cartilage thickness predicted by individual variations in joint loading. Knee magnetic resonance (MR) images and the peak knee adduction moments during walking were obtained from 11 young healthy male subjects (age 30.5+/-5.1 years). The cartilage thicknesses and surface radii of the femoral and tibial cartilage were measured in the weight-bearing regions of the medial and lateral compartments of three-dimensional models from the MR images. The ratio of contact pressure between the medial and lateral compartments was calculated from the radii of tibiofemoral contact surface geometries. The results showed that the medial to lateral pressure ratios were not correlated with the medial to lateral cartilage thickness ratios. However, in general, pressure was higher in the lateral than medial compartments and cartilage was thicker in the lateral than medial compartments. The peak knee adduction moment showed a significant positive linear correlation with medial to lateral thickness ratio in both femur (R(2)=0.43,P<0.01) and tibia (R(2)=0.32,P<0.01). The results of this study suggest that the dynamics of walking is an important factor to describe individual differences in cartilage thickness for normal subjects.     

Effects of immobilization for 6 weeks on rabbit knee articular surfaces as assessed by the semiquantitative stereomicroscopic method

The effects of a 6-week immobilization period on rabbit knee articular cartilage surfaces were investigated by a new semiquantitative stereomicroscopic method following ink staining and processing for scanning electron microscopy. All surfaces of the immobilized knee joint were affected and displayed significant degenerative alterations. The knee joint contralateral to the immobilized one exhibited slight changes which could be interpreted as a sign of altered loading after immobilization. Articular surfaces of the patella and lateral condyle of the femur proved to be best suited for surface analysis on account of the small size, distinct borders and inherent evenness of the cartilage in non-treated animals.     

Proteoglycan 4 downregulation in a sheep meniscectomy model of early osteoarthritis

Osteoarthritis is a disease of multifactorial aetiology characterised by progressive breakdown of articular cartilage. In the early stages of the disease, changes become apparent in the superficial zone of articular cartilage, including fibrillation and fissuring. Normally, a monolayer of lubricating molecules is adsorbed on the surface of cartilage and contributes to the minimal friction and wear properties of synovial joints. Proteoglycan 4 is the lubricating glycoprotein believed to be primarily responsible for this boundary lubrication. Here we have used an established ovine meniscectomy model of osteoarthritis, in which typical degenerative changes are observed in the operated knee joints at three months after surgery, to evaluate alterations in proteoglycan 4 expression and localisation in the early phases of the disease. In normal control joints, proteoglycan 4 was immunolocalised in the superficial zone of cartilage, particularly in those regions of the knee joint covered by a meniscus. After the onset of early osteoarthritis, we demonstrated a loss of cellular proteoglycan 4 immunostaining in degenerative articular cartilage, accompanied by a significant (p < 0.01) decrease in corresponding mRNA levels. Early loss of proteoglycan 4 from the cartilage surface in association with a decrease in its expression by superficial-zone chondrocytes might have a role in the pathogenesis of osteoarthritis.     

Considerations on Joint and Articular Cartilage Mechanics

When studying joint degeneration leading to osteoarthritis (OA), it seems imperative that local joint tissue loading is known during normal everyday movement and that the adaptive/degenerative effects of this loading are quantified systematically. Philosophically, we believe the best way to approach this problem is by studying joint degeneration and osteoarthritis in long-term experimental models and by representing diarthrodial joints and the associated tissues with accurate, geometric and structural, theoretical models. Here, we present selected examples of our work representing this approach. Experimentally, we demonstrate that the local loading of joints changes continuously in experimental models of OA, not only because of the changing external and internal loading, but also because of the continuous alterations in joint contact geometry and tissue mechanical properties. Furthermore, we show that single bouts of joint loading affect gene expression, and that gene expression, as well as subsequent joint degeneration is site-specific. In fact, opposing articular surfaces that are exposed to the same loading may degenerate at completely different rates. Finally, we propose a series of theoretical models of articular cartilage and contact mechanics, demonstrating that many of the anisotropic and inhomogeneous properties can be explained by structural elements and their orientation and volumetric concentration across the tissue.     

The low permeability of healthy meniscus and labrum limit articular cartilage consolidation and maintain fluid load support in the knee and hip

The knee meniscus and hip labrum appear to be important for joint health, but the mechanisms by which these structures perform their functions are not fully understood. The fluid phase of articular cartilage provides compressive stiffness and aids in maintaining a low friction articulation. Healthy fibrocartilage, the tissue of meniscus and labrum, has a lower fluid permeability than articular cartilage. In this study we hypothesized that an important function of the knee meniscus and the hip labrum is to augment fluid retention in the articular cartilage of a mechanically loaded joint. Axisymmetric hyperporoelastic finite element models were analyzed for an idealized knee and an idealized hip. The results indicate that the meniscus maintained fluid pressure and inhibited fluid exudation in knee articular cartilage. Similar, but smaller, effects were seen with the labrum in the hip. Increasing the fibrocartilage permeability relative to that of articular cartilage gave a consolidation rate and loss of fluid load support comparable to that predicted by meniscectomy or labrectomy. The reduced articular cartilage fluid pressure that was calculated for the joint periphery is consistent with patterns of endochondral ossification and osteophyte formation in knee and hip osteoarthritis. High articular central strains and loss of fluid load support after meniscectomy could lead to fibrillation. An intact low-permeability fibrocartilage is important for limiting fluid exudation from articular cartilage in the hip and knee. This may be an important aspect of the role of fibrocartilage in protecting these joints from osteoarthritis.     

Knee joint kinematics during walking influences the spatial cartilage thickness distribution in the knee

The regional adaptation of knee cartilage morphology to the kinematics of walking has been suggested as an important factor in the evaluation of the consequences of alteration in normal gait leading to osteoarthritis. The purpose of this study was to investigate the association of spatial cartilage thickness distributions of the femur and tibia in the knee to the knee kinematics during walking. Gait data and knee MR images were obtained from 17 healthy volunteers (age 33.2 ± 9.8 years). Cartilage thickness maps were created for the femoral and tibial cartilage. Locations of thickest cartilage in the medial and lateral compartments in the femur and tibia were identified using a numerical method. The flexion-extension (FE) angle associated with the cartilage contact regions on the femur, and the anterior-posterior (AP) translation and internal-external (IE) rotation associated with the cartilage contact regions on the tibia at the heel strike of walking were tested for correlation with the locations of thickest cartilage. The locations of the thickest cartilage had relatively large variation (SD, 8.9°) and was significantly associated with the FE angle at heel strike only in the medial femoral condyle (R(2)=0.41, p<0.01). The natural knee kinematics and contact surface shapes seem to affect the functional adaptation of knee articular cartilage morphology. The sensitivity of cartilage morphology to kinematics at the knee during walking suggests that regional cartilage thickness variations are influenced by both loading and the number of loading cycles. Thus walking is an important consideration in the analysis of the morphological variations of articular cartilage, since it is the dominant cyclic activity of daily living. The sensitivity of cartilage morphology to gait kinematics is also important in understanding the etiology and pathomechanics of osteoarthritis.     

Articular cartilage in the knee joint of the African elephant, Loxodonta africana, Blumenbach 1797

Knee joints of one adult and three juvenile African elephants were dissected. The specific features of the articular cartilage with particular reference to matrix components were studied by light and electron microscopy and immunohistochemistry. The elephant knee joint cartilage contains an unusually low concentration of proteoglycans resulting in rather eosinophilic staining properties of the matrix. The very thick collagen fibers of the cartilage possibly represent collagen I. Except for the different thickness of cartilage at the weight-bearing surfaces of femur (approximately 6.7 mm) and tibia (approximately 11.2 mm) in juvenile elephants, light and electron microscopy did not reveal distinct topographical differences in cartilage structure, perhaps because of the high congruency of the articulating surfaces and resulting uniform load distribution in the knee. The number of cell profiles per section area of both femoral (approximately 950 cell profiles/mm(2)) and tibial cartilage (approximately 898 cell profiles/mm(2)) was low, indicating excessive matrix production by the chondrocytes during cartilage development. These unique properties could be a result of the enormous compressive load resting on the elephant knee. Maintenance of the equilibrium between biological function and resistance to compression seems to be crucial in the elephant knee joint cartilage. Any disturbance that interferes with this equilibrium appears to lead to arthrotic alterations, as particularly seen in captive elephants.     

A Mathematical Formulation for 3D Quasi-Static Multibody Models of Diarthrodial Joints

This study describes a genera] set of equations for quasi-static analysis of three-dimensional multibody systems, with a particular emphasis on modeling of diarthrodial joints. The model includes articular contact, muscle forces, tendons and tendon pulleys, ligaments, and the wrapping of soft tissue structures around bone and cartilage surfaces. The general set of equations governing this problem are derived using a consistent notation for all types of links, which can be converted conveniently into efficient computer codes. The computational efficiency of the model is enhanced by the use of analytical Jacobians, particularly in the analysis of articular surface contact and wrapping of soft tissue structures around bone and cartilage surfaces. The usefulness of the multibody model is demonstrated by modeling the patellofemoral joint of six cadaver knees, using cadaver-specific data for the articular surface and bone geometries, as well as tendon and ligament insertions and muscle lines of actions. Good accuracy was observed when comparing the model patellar kinematic predictions to experimental data (mean ± stand, dev. error in translation: 0.63 ± 1.19 mm, 0.10 ± 0.71 mm, -0.29 ± 0.84 mm along medial, proximal, and anterior directions, respectively; in rotation: -1.41 ± 1.71°, 0.27 ±2.38°, -1.13 ± 1.83° in flexion, tilt and rotation, respectively). The accuracy which can be achieved with this type of model, and the computational efficiency of the algorithm employed in this study may serve in many applications such as computer-aided surgical planning, and real-time computer-assisted surgery in the operating room.