A three-dimensional finite element analysis of the combined behavior of ligaments and menisci in the healthy human knee joint

We present here a three-dimensional FE model of the healthy human knee that included the main structures of the joint: bones, all the relevant ligaments and patellar tendon, menisci and articular cartilages. Bones were considered to be rigid, articular cartilage and menisci linearly elastic, isotropic and homogeneous and ligaments hyperelastic and transversely isotropic. Initial strains on the ligaments and patellar tendon were also considered. This model was validated using experimental and numerical results obtained by other authors. Our main goal was to analyze the combined role of menisci and ligaments in load transmission and stability of the human knee. The results obtained reproduce the complex, nonuniform stress and strain fields that occur in the biological soft tissues involved and the kinematics of the human knee joint under a physiological external load.     

Partial meniscectomy changes fluid pressurization in articular cartilage in human knees

Partial meniscectomy is believed to change the biomechanics of the knee joint through alterations in the contact of articular cartilages and menisci. Although fluid pressure plays an important role in the load support mechanism of the knee, the fluid pressurization in the cartilages and menisci has been ignored in the finite element studies of the mechanics of meniscectomy. In the present study, a 3D fibril-reinforced poromechanical model of the knee joint was used to explore the fluid flow dependent changes in articular cartilage following partial medial and lateral meniscectomies. Six partial longitudinal meniscectomies were considered under relaxation, simple creep, and combined creep loading conditions. In comparison to the intact knee, partial meniscectomy not only caused a substantial increase in the maximum fluid pressure but also shifted the location of this pressure in the femoral cartilage. Furthermore, these changes were positively correlated to the size of meniscal resection. While in the intact joint, the location of the maximum fluid pressure was dependent on the loading conditions, in the meniscectomized joint the location was predominantly determined by the site of meniscal resection. The partial meniscectomy also reduced the rate of the pressure dissipation, resulting in even larger difference between creep and relaxation times as compared to the case of the intact knee. The knee joint became stiffer after meniscectomy because of higher fluid pressure at knee compression followed by slower pressure dissipation. The present study indicated the role of fluid pressurization in the altered mechanics of meniscectomized knees.     

Tensile properties, collagen content, and crosslinks in connective tissues of the immature knee joint

Background

The major connective tissues of the knee joint act in concert during locomotion to provide joint stability, smooth articulation, shock absorption, and distribution of mechanical stresses. These functions are largely conferred by the intrinsic material properties of the tissues, which are in turn determined by biochemical composition. A thorough understanding of the structure-function relationships of the connective tissues of the knee joint is needed to provide design parameters for efforts in tissue engineering.

Methodology/Principal Findings

The objective of this study was to perform a comprehensive characterization of the tensile properties, collagen content, and pyridinoline crosslink abundance of condylar cartilage, patellar cartilage, medial and lateral menisci, cranial and caudal cruciate ligaments (analogous to anterior and posterior cruciate ligaments in humans, respectively), medial and lateral collateral ligaments, and patellar ligament from immature bovine calves. Tensile stiffness and strength were greatest in the menisci and patellar ligament, and lowest in the hyaline cartilages and cruciate ligaments; these tensile results reflected trends in collagen content. Pyridinoline crosslinks were found in every tissue despite the relative immaturity of the joints, and significant differences were observed among tissues. Notably, for the cruciate ligaments and patellar ligament, crosslink density appeared more important in determining tensile stiffness than collagen content.

Conclusions/Significance

To our knowledge, this study is the first to examine tensile properties, collagen content, and pyridinoline crosslink abundance in a direct head-to-head comparison among all of the major connective tissues of the knee. This is also the first study to report results for pyridinoline crosslink density that suggest its preferential role over collagen in determining tensile stiffness for certain tissues.     

Role of cartilage collagen fibrils networks in knee joint biomechanics under compression

Collagen fibrils networks in knee cartilage and menisci change in content and structure from a region to another. While resisting tension, they influence global joint response as well as local strains particularly at short-term periods. To investigate the role of fibrils networks in knee joint mechanics and in particular cartilage response, a novel model of the knee joint is developed that incorporates the cartilage and meniscus fibrils networks as well as depth-dependent properties in cartilage. The joint response under up to 2000 N compression is investigated for conditions simulating the absence in cartilage of deep fibrils normal to subchondral bone or superficial fibrils parallel to surface as well as localized split of cartilage at subchondral junction or localized damage to superficial fibrils at loaded areas. Deep vertical fibrils network in cartilage play a crucial role in stiffening (by 10%) global response and protecting cartilage by reducing large strains (from maximum of 102% to 38%), in particular at subchondral junction. Superficial horizontal fibrils protect the tissue mainly from excessive strains at superficial layers (from 27% to 8%). Local cartilage split at base disrupts the normal function of vertical fibrils at the affected areas resulting in higher strains.Deep fibrils, and to a lesser extent superficial fibrils, play dominant mechanical roles in cartilage response under transient compression. Any treatment modality attempting to repair or regenerate cartilage defects involving partial or full thickness osteochondral grafts should account for the crucial role of collagen fibrils networks and the demanding mechanical environment of the tissue.     

Comparison of MRI-based estimates of articular cartilage contact area in the tibiofemoral joint

Knee osteoarthritis (OA) detrimentally impacts the lives of millions of older Americans through pain and decreased functional ability. Unfortunately, the pathomechanics and associated deviations from joint homeostasis that OA patients experience are not well understood. Alterations in mechanical stress in the knee joint may play an essential role in OA; however, existing literature in this area is limited. The purpose of this study was to evaluate the ability of an existing magnetic resonance imaging (MRI)-based modeling method to estimate articular cartilage contact area in vivo. Imaging data of both knees were collected on a single subject with no history of knee pathology at three knee flexion angles. Intra-observer reliability and sensitivity studies were also performed to determine the role of operator-influenced elements of the data processing on the results. The method's articular cartilage contact area estimates were compared with existing contact area estimates in the literature. The method demonstrated an intra-observer reliability of 0.95 when assessed using Pearson's correlation coefficient and was found to be most sensitive to changes in the cartilage tracings on the peripheries of the compartment. The articular cartilage contact area estimates at full extension were similar to those reported in the literature. The relationships between tibiofemoral articular cartilage contact area and knee flexion were also qualitatively and quantitatively similar to those previously reported. The MRI-based knee modeling method was found to have high intra-observer reliability, sensitivity to peripheral articular cartilage tracings, and agreeability with previous investigations when using data from a single healthy adult. Future studies will implement this modeling method to investigate the role that mechanical stress may play in progression of knee OA through estimation of articular cartilage contact area.     

A validated three-dimensional computational model of a human knee joint

This paper presents a three-dimensional finite element tibio-femoral joint model of a human knee that was validated using experimental data. The geometry of the joint model was obtained from magnetic resonance (MR) images of a cadaveric knee specimen. The same specimen was biomechanically tested using a robotic/universal force-moment sensor (UFS) system and knee kinematic data under anterior-posterior tibial loads (up to 100 N) were obtained. In the finite element model (FEM), cartilage was modeled as an elastic material, ligaments were represented as nonlinear elastic springs, and menisci were simulated by equivalent-resistance springs. Reference lengths (zero-load lengths) of the ligaments and stiffness of the meniscus springs were estimated using an optimization procedure that involved the minimization of the differences between the kinematics predicted by the model and those obtained experimentally. The joint kinematics and in-situ forces in the ligaments in response to axial tibial moments of up to 10 Nm were calculated using the model and were compared with published experimental data on knee specimens. It was also demonstrated that the equivalent-resistance springs representing the menisci are important for accurate calculation of knee kinematics. Thus, the methodology developed in this study can be a valuable tool for further analysis of knee joint function and could serve as a step toward the development of more advanced computational knee models.     

Stresses and strains in the medial meniscus of an ACL deficient knee under anterior loading: a finite element analysis with image-based experimental validation

The menisci are believed to play a stabilizing role in the ACL-deficient knee, and are known to be at risk for degradation in the chronically unstable knee. Much of our understanding of this behavior is based on ex vivo experiments or clinical studies in which we must infer the function of the menisci from external measures of knee motion. More recently, studies using magnetic resonance (MR) imaging have provided more clear visualization of the motion and deformation of the menisci within the tibio-femoral articulation. In this study, we used such images to generate a finite element model of the medial compartment of an ACL-deficient knee to reproduce the meniscal position under anterior loads of 45, 76, and 107 N. Comparisons of the model predictions to boundaries digitized from images acquired in the loaded states demonstrated general agreement, with errors localized to the anterior and posterior regions of the meniscus, areas in which large shear stresses were present. Our model results suggest that further attention is needed to characterize material properties of the peripheral and horn attachments. Although overall translation of the meniscus was predicted well, the changes in curvature and distortion of the meniscus in the posterior region were not captured by the model, suggesting the need for refinement of meniscal tissue properties.     

Statistical shape modeling describes variation in tibia and femur surface geometry between Control and Incidence groups from the Osteoarthritis Initiative database

We hypothesize that variability in knee subchondral bone surface geometry will differentiate between patients at risk and those not at risk for developing osteoarthritis (OA) and suggest that statistical shape modeling (SSM) methods form the basis for developing a diagnostic tool for predicting the onset of OA. Using a subset of clinical knee MRI data from the osteoarthritis initiative (OAI), the objectives of this study were to (1) utilize SSM to compactly and efficiently describe variability in knee subchondral bone surface geometry and (2) determine the efficacy of SSM and rigid body transformations to distinguish between patients who are not expected to develop osteoarthritis (i.e. Control group) and those with clinical risk factors for OA (i.e. Incidence group). Quantitative differences in femur and tibia surface geometry were demonstrated between groups, although differences in knee joint alignment measures were not statistically significant, suggesting that variability in individual bone geometry may play a greater role in determining joint space geometry and mechanics. SSM provides a means of explicitly describing complete articular surface geometry and allows the complex spatial variation in joint surface geometry and joint congruence between healthy subjects and those with clinical risk of developing or existing signs of OA to be statistically demonstrated.     

In-vitro measurement of static pressure distribution in synovial joints--Part I: Tibial surface of the knee

In this first part of a two-part paper, the results of measurement of static pressure distribution on the tibial surface of the knee are presented. Results with intact menisci have been obtained from 18 specimens. Eight of these specimens were the subject of further measurements following medial meniscectomy. The study has been carried out at various flexion angles of the knee with the joint subjected to a compressive force, with or without an initial passive relative displacement between the joint members. The results indicate that a significant fraction of the joint compressive load is transmitted through the menisci and that total meniscectomy causes a drastic alteration in the pressure distribution on the tibial surface. Clinical implications of these results, in terms of post-meniscectomy degenerative changes and mechanism of meniscal lesions, have been discussed.     

Scanning electron microscopy study of the meniscus of the knee in patients with anterior cruciate ligament lesions]

In the aim of bringing a contribution to role of the knee menisci and the functional connection between meniscal lesions and knee joint instability, four patients have been studied, who underwent arthroscopy for sub-acute tear of anterior cruciate ligament without clinical or morphological evidence of meniscal pathology. In these patients biopsies have been taken from one of the menisci and processed for the examination by the SEM. As control, meniscal fragments from two healthy knees have been studied from patients who underwent amputation at thigh for accidental trauma with irreparable lesion of femoral artery. In patients affected by ligamentous tear, on the meniscal surface a lot of deposited material appears, as well as many microlesions as clefts or cracking and distortion of superficial collagenous fibers. All described alteration are more evident in the central portion of menisci than in the anterior or posterior horns. The above mentioned patterns suggest a strong correlation of the knee instability due to ligamentous lesions and meniscal degenerative process which would onset before its clinical or macroscopical evidence.     

An emerging player in knee osteoarthritis: the infrapatellar fat pad

The role of inflammation in the development, progression, and clinical features of osteoarthritis has become an area of intense research in recent years. This led to the recognition of synovitis as an important source of inflammation in the joint and indicated that synovitis is intimately associated with pain and osteoarthritis progression. In this review, we discuss another emerging source of inflammation that could play a role in disease development/progression: the infrapatellar fat pad (IFP). The aim of this review is to offer a comprehensive view of the pathology of IFP as obtained from magnetic resonance studies, along with its characterization at both the cellular and the molecular level. Furthermore, we discuss the possible function of this organ in the pathological processes in the knee by summarizing the knowledge regarding the interactions between IFP and other joint tissues and discussing the pro- versus anti-inflammatory functions this tissue could have. We hope that this review will offer an overview of all published data regarding the IFP and will indicate novel directions for future research.     

The nuclear oestrogen receptor in the female rat. Effects of oestradiol administration during the oestrous cycle on the uterus and contrasting effects of progesterone on the uterus and hypothalamus.

The semilunar menisci of the knee have an important mechanical function and are commonly involved in joint degeneration. However, previously published analyses of the compositions of normal and degenerate human menisci vary widely. In the present study the glycosaminoglycan content and composition of selected areas of the menisci of eight normal knees of working foxhounds were determined. The menisci contained 10% less water and abut 8-fold less glucosaminoglycan than did the articular cartilage of these animals. Although the glycosaminoglycan composition was the same in different regions of the menisci, the total amounts varied considerably. Of the chondroitinase digestible material, approx. 60% was chondroitin 6-sulphate, 25% chondroitin 4-sulphate, 10% chondroitin and 5% dermatan sulphate. Hyaluronic acid accounted for about 6% of the total uronic acid.     

Running kinematics and shock absorption do not change after brief exhaustive running

Because of the nature of running, the forces encountered require a proper coordination of joint action of the lower extremity to dissipate the ground reaction forces and accelerations through the kinetic chain. Running-related muscle fatigue may reduce the shock absorbing capacity of the lower extremity and alter running kinematics. The purpose of this study was to determine if a bout of exhaustive running at a physiologically determined high intensity, changes running kinematics, impact accelerations, and alters shock attenuating capabilities. It was hypothesized that as a result of fatigue induced by an exhaustive run, running kinematics, impact accelerations at the head and shank, acceleration reduction, and shock attenuation would change. A within-subject, repeated-measures design was used for this study. Twelve healthy, competitive male and female distance runners participated. Subjects performed 2 testing sessions consisting of a VO2max treadmill protocol to determine the heart rate at ventilatory threshold and a fatigue-inducing running bout at the identified ventilatory threshold heart rate. Kinematic data included knee flexion, pronation, time to maximum knee flexion, and time to maximum pronation. Acceleration data included shank acceleration, head acceleration, and shock attenuation. No significant differences resulted for the kinematic or acceleration variables. Although the results of this study do not support the original hypotheses, the influence of running fatigue on kinematics and accelerations remains inconclusive. Future research is necessary to examine fatigue-induced changes in running kinematics and accelerations and to determine the threshold at which point the changes may occur.     

Alterations in structure and properties of collagen network of osteoarthritic and repaired cartilage modify knee joint stresses

Organization of the collagen network is known to be different in healthy, osteoarthritic and repaired cartilage. The aim of the study was to investigate how the structure and properties of collagen network of cartilage modulate stresses in a knee joint with osteoarthritis or cartilage repair. Magnetic resonance imaging (MRI) at 1.5 T was conducted for a knee joint of a male subject. Articular cartilage and menisci in the knee joint were segmented, and a finite element mesh was constructed based on the two-dimensional section in sagittal projection. Then, the knee joint stresses were simulated under impact loads by implementing the structure and properties of healthy, osteoarthritic and repaired cartilage in the models. During the progression of osteoarthritis, characterized especially by the progressive increase in the collagen fibrillation from the superficial to the deeper layers, the stresses were reduced in the superficial zone of cartilage, while they were increased in and under menisci. Increased fibril network stiffness of repair tissue with randomly organized collagen fibril network reduced the peak stresses in the adjacent tissue and strains at the repair–adjacent cartilage interface. High collagen fibril strains were indicative of stress concentration areas in osteoarthritic and repaired cartilage. The collagen network orientation and stiffness controlled the stress distributions in healthy, osteoarthritic and repaired cartilage. The evaluation of articular cartilage function using clinical MRI and biomechanical modeling could enable noninvasive estimation of osteoarthritis progression and monitoring of cartilage repair. This study presents a step toward those goals.     

Systemic hypoxia alters gene expression levels of structural proteins and growth factors in knee joint cartilage

We investigated the effects of short- (8- and 24-h) and long-term (3 weeks) exposure to systemic normobaric hypoxia (13%) on the gene expression level of structural proteins and growth factors in knee joint cartilage of rabbits. Collagen type Ia2, II, and Va1, TGF-beta1, and b-FGF were upregulated after short-term hypoxia in both menisci, but not in articular cartilage. In contrast, long-term hypoxia downregulated gene expression level of collagens, aggrecan, and growth factors in articular cartilage and meniscal fibrocartilage. Interestingly, gene expression levels of non-collagenous proteins biglycan, decorin, and versican were not affected by short-term or by long-term hypoxia in knee joint cartilage. The present study suggests that changes in oxygen level differentially affect gene expression levels of growth factors, collagens, and non-collagenous proteins in normal knee joint cartilage in rabbits.     

3D finite element model of meniscectomy: changes in joint contact behavior

The goal of this study is to quantify changes in knee joint contact behavior following varying degrees of the medial partial meniscectomy. A previously validated 3D finite element model was used to simulate 11 different meniscectomies. The accompanying changes in the contact pressure on the superior surface of the menisci and tibial plateau were quantified as was the axial strain in the menisci and articular cartilage. The percentage of medial meniscus removed was linearly correlated with maximum contact pressure, mean contact pressure, and contact area. The lateral hemi-joint was minimally affected by the simulated medial meniscectomies. The location of maximum strain and location of maximum contact pressure did not change with varying degrees of partial medial meniscectomy. When 60% of the medial meniscus was removed, contact pressures increased 65% on the remaining medial meniscus and 55% on the medial tibial plateau. These data will be helpful for assessing potential complications with the surgical treatment of meniscal tears. Additionally, these data provide insight into the role of mechanical loading in the etiology of post-meniscectomy osteoarthritis.     

Radial fibre proportions in human knee joint menisci. Measurement by scanning optical microscopy

The proportions of medial and lateral knee joint menisci represented by radially orientated collagen (COL) were measured in 42 specimens from 24 hospital patients examined post-mortem. Images of the fibre bundles were obtained by the 488-nm laser confocal scanning of hydrated, fixed radial blocks taken from the anterior, middle and posterior regions of the menisci after staining with picro-Sirius red. Measurements of the percentage of each image occupied by fluorescent, doubly refractile COL were made by means of a Kontron IBAS image analyser, after interactive segmentation. In areas adjoining the outer, lateral parts of both the medial and lateral menisci, the proportion of all samples identified as radial COL was 7.56 +/- 0.28%. The corresponding figure for areas near the inner, medial edges of the menisci was 17.80 +/- 0.80%. However, no relationship was demonstrable between age and sex and meniscal radial fibre optical density, and there was no difference between the proportion of radial fibres in the anterior, middle or posterior regions.     

Effects of a viscosupplementation therapy on rabbit menisci in an anterior cruciate ligament transection model of osteoarthritis

The aim of this study was to evaluate the morphological, microstructural, and mechanical effects of a viscosupplementation therapy on rabbit menisci at an early stage of osteoarthritis (OA). Anterior cruciate ligament transection (ACLT) was performed in twelve male New-Zealand White rabbits on the right knee joint. Six of these twelve rabbits received a mono intra-articular injection of high molecular weight hyaluronic acid (HA) two weeks after ACLT. Six additional healthy rabbits served as controls. Medial menisci were removed from all right knees (n = 18) six weeks after ACLT and were graded macroscopically. Indentation-relaxation tests were performed in the anterior and posterior regions of the menisci. Collagen fiber organization and glycosaminoglycan (GAG) content were assessed by biphotonic confocal microscopy and histology, respectively. Viscosupplementation significantly (p = 0.002) improved the surface integrity of the medial menisci compared to the operated non-treated group. Moreover, the injection seems to have an effect on the GAG distribution in the anterior region of the menisci. However, the viscoelastic properties of both operated groups were similar and significantly lower than those of the healthy group, which was explained by their modified collagen fiber organization. They displayed disruption of the tie fibers due to structural alterations of the superficial layers from which they emanate, leading to modifications in the deep zone. To conclude, the viscosupplementation therapy prevents macroscopic lesions of the menisci, but it fails to restore their collagen fiber organization and their viscoelastic properties. This finding supports the role of this treatment in improving the lubrication over the knee.     

The effect of kinematic and kinetic changes on meniscal strains during gait

The menisci play an important role in load distribution, load bearing, joint stability, lubrication, and proprioception. Partial meniscectomy has been shown to result in changes in the kinematics and kinetics at the knee during gait that can lead to progressive meniscal degeneration. This study examined changes in the strains within the menisci associated with kinematic and kinetic changes during the gait cycle. The gait changes considered were a 5 deg shift toward external rotation of the tibia with respect to the femur and an increased medial-lateral load ratio representing an increased adduction moment. A finite element model of the knee was developed and tested using a cadaveric specimen. The cadaver was placed in positions representing heel-strike and midstance of the normal gait, and magnetic resonance images were taken. Comparisons of the model predictions to boundaries digitized from images acquired in the loaded states were within the errors produced by a 1 pixel shift of either meniscus. The finite element model predicted that an increased adduction moment caused increased strains of both the anterior and posterior horns of the medial meniscus. The lateral meniscus exhibited much lower strains and had minimal changes under the various loading conditions. The external tibial rotational change resulted in a 20% decrease in the strains in the posterior medial horn and increased strains in the anterior medial horn. The results of this study suggest that the shift toward external tibial rotation seen clinically after partial medial meniscectomy is not likely to cause subsequent degenerative medial meniscal damage, but the consequence of this kinematic shift on the pathogenesis of osteoarthritis following meniscectomy requires further consideration.     

Experimentally reduced hip abductor function during walking: Implications for knee joint loads

Hip and knee functions are intimately connected and reduced hip abductor function might play a role in development of knee osteoarthritis (OA) by increasing the external knee adduction moment during walking. The purpose of this study was to test the hypothesis that reduced function of the gluteus medius (GM) muscle would lead to increased external knee adduction moment during level walking in healthy subjects. Reduced GM muscle function was induced experimentally, by means of intramuscular injections of hypertonic saline that produced an intense short-term muscle pain and reduced muscle function. Isotonic saline injections were used as non-painful control. Fifteen healthy subjects performed walking trials at their self-selected walking speed before and immediately after injections, and again after 20 min of rest, to ensure pain recovery. Standard gait analyses were used to calculate three-dimensional trunk and lower extremity joint kinematics and kinetics. Surface electromyography (EMG) of the glutei, quadriceps, and hamstring muscles were also measured. The peak GM EMG activity had temporal concurrence with peaks in frontal plane moments at both hip and knee joints. The EMG activity in the GM muscle was significantly reduced by pain (?39.6%). All other muscles were unaffected. Peaks in the frontal plane hip and knee joint moments were significantly reduced during pain (?6.4% and ?4.2%, respectively). Lateral trunk lean angles and midstance hip joint adduction and knee joint extension angles were reduced by ?1°. Thus, the gait changes were primarily caused by reduced GM function. Walking with impaired GM muscle function due to pain significantly reduced the external knee adduction moment. This study challenge the notion that reduced GM function due to pain would lead to increased loads at the knee joint during level walking.