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  Magnetic resonance (MR) imaging has been widely used to evaluate the thickness and volume of articular cartilage both in vivo and in vitro. While morphological information on the cartilage can be obtained using MR images, image processing for extracting geometric boundaries of the cartilage may introduce variations in the thickness of the cartilage. To evaluate the variability of using MR images to construct finite element (FE) knee cartilage models, five investigators independently digitized the same set of MR images of a human knee. The topology of cartilage thickness was determined using a minimal distance algorithm. Less than 8 percent variation in cartilage thickness was observed from the digitized data. The effect of changes in cartilage thickness on contact stress analysis was then investigated using five FE models of the knee. One FE model (average FE model) was constructed using the mean values of the digitized contours of the cartilage, and the other four were constructed by varying the thickness of the average FE model by +/- 5 percent and +/- 10 percent, respectively. The results demonstrated that under axial tibial compressive loading (up to 1,400 N), variations of cartilage thickness caused by digitization of MR images may result in a difference of approximately 10 percent in peak contact stresses (surface pressure, von Mises stress, and hydrostatic pressure) in the cartilage. A reduction of cartilage thickness caused increases of contact stresses, while an increase of cartilage thickness reduced contact stresses. Furthermore, the effect of variation of material properties of the cartilage on contact stress analysis was investigated. The peak contact stress increased almost linearly with the Young's modulus of the cartilage. The peak von Mises stress was dramatically reduced when the Poisson,s ratio was increased from 0.05 to 0.49 under an axial compressive load of 1,400 N, while peak hydrostatic pressure was dramatically increased. Peak surface pressure was also increased with the Poisson's ratio, but with a lower magnitude compared to von Mises stress and hydrostatic pressure. In conclusion, the imaging process may cause 10 percent variations in peak contact stress, and the predicted stress distribution is sensitive to the accuracy of the material properties of the cartilage model, especially to the variation of Poisson's ratio.


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  Variability of a three-dimensional finite element model constructed using magnetic resonance images of a knee for joint contact stress analysis


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  Cryopreservation has numerous practical applications in medicine, biotechnology, agriculture, forestry, aquaculture and biodiversity conservation, with huge potentials for biological cell and tissue banking. A specific tissue of interest for cryopreservation is the articular cartilage of the human knee joint for two major reasons: (1) clinically, there exists an untapped potential for cryopreserved cartilage to be used in surgical repair/reconstruction/replacement of injured joints because of the limited availability of fresh donor tissue and, (2) scientifically, successful cryopreservation of cartilage, an avascular tissue with only one cell type, is considered a stepping stone for transition from biobanking cell suspensions and small tissue slices to larger and more complicated tissues. For more than 50years, a great deal of effort has been directed toward understanding and overcoming the challenges of cartilage preservation. In this article, we focus mainly on studies that led to the finding that vitrification is an appropriate approach toward successful preservation of cartilage. This is followed by a review of the studies on the main challenges of vitrification, i.e. toxicity and diffusion, and the novel approaches to overcome these challenges such as liquidus tracking, diffusion modeling, and cryoprotective agent cocktails, which have resulted in the recent advancements in the field.


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  http://ac.els-cdn.com/S0011224013001089/1-s2.0-S0011224013001089-main.pdf?_tid=3c2cb576-902e-11e7-8e23-00000aab0f6c&acdnat=1504391571_b3480b2b58acc8458c6c59c62d6dbec8


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  This biomechanical study reports strain gradients in patellofemoral joint cross-sections of seven porcine specimens in response to 1% unconfined axial compression subsequent to specific amounts of off-set strain. Strain distributions were quantified with a customized laser-based electronic speckle pattern interferometry (ESPI) system in a non-contact manner, delivering high-resolution, high-sensitivity strain maps over entire patellofemoral cartilage cross-sections. Strain reports were evaluated to determine differences in strain magnitudes between the superficial, middle, and deep cartilage layers in femoral and patellar cartilage. In addition, the effect of 5%, 10%, 15%, and 20% off-set strain on depth-dependent strain gradients was quantified. Regardless of the amount of off-set strain, the superficial layer of femoral cartilage absorbed the most strain, and the deep layer absorbed the least strain. These depth-dependent strain gradients were most pronounced for 5% off-set strain, at which the superficial layer absorbed on average 5.7 and 23.7 times more strain as compared to the middle and deep layers, respectively. For increased off-set strain levels, strain gradients became less pronounced. At 20% off-set strain, differences in layer-specific strain were not statistically significant, with the superficial layer showing a 1.4 fold higher strain as the deep layer. Patellar cartilage exhibited similar strain gradients and effects of off-set strain, although the patellar strain was on average 19% larger as compared to corresponding femoral strain reports. This study quantified for the first time continuous strain gradients over patellofemoral cartilage cross-sections. Next to provision of a detailed functional characterization of normal diarthrodial joints, this novel experimental approach holds considerable attraction to investigate joint degenerative processes.


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  Load-bearing characteristics of articular cartilage are impaired during tissue degeneration. Quantitative microscopy enables in vitro investigation of cartilage structure but determination of tissue functional properties necessitates experimental mechanical testing. The fibril-reinforced poroviscoelastic (FRPVE) model has been used successfully for estimation of cartilage mechanical properties. The model includes realistic collagen network architecture, as shown by microscopic imaging techniques. The aim of the present study was to investigate the relationships between the cartilage proteoglycan (PG) and collagen content as assessed by quantitative microscopic findings, and model-based mechanical parameters of the tissue. Site-specific variation of the collagen network moduli, PG matrix modulus and permeability was analyzed. Cylindrical cartilage samples (n=22) were harvested from various sites of the bovine knee and shoulder joints. Collagen orientation, as quantitated by polarized light microscopy, was incorporated into the finite-element model. Stepwise stress-relaxation experiments in unconfined compression were conducted for the samples, and sample-specific models were fitted to the experimental data in order to determine values of the model parameters. For comparison, Fourier transform infrared imaging and digital densitometry were used for the determination of collagen and PG content in the same samples, respectively. The initial and strain-dependent fibril network moduli as well as the initial permeability correlated significantly with the tissue collagen content. The equilibrium Young's modulus of the nonfibrillar matrix and the strain dependency of permeability were significantly associated with the tissue PG content. The present study demonstrates that modern quantitative microscopic methods in combination with the FRPVE model are feasible methods to characterize the structure-function relationships of articular cartilage.


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  Characterization of articular cartilage by combining microscopic analysis with a fibril-reinforced finite-element model


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  Nonlinear, linear and failure properties of articular cartilage and meniscus in opposing contact surfaces are poorly known in tension. Relationships between the tensile properties of articular cartilage and meniscus in contact with each other within knee joints are also not known. In the present study, rectangular samples were prepared from the superficial lateral femoral condyle cartilage and lateral meniscus of bovine knee joints. Tensile tests were carried out with a loading rate of 5mm/min until the tissue rupture. Nonlinear properties of the toe region, linear properties in larger strains, and failure properties of both tissues were analysed. The strain-dependent tensile modulus of the toe region, Young's modulus of the linear region, ultimate tensile stress and toughness were on average 98.2, 8.3, 4.0 and 1.9 times greater (p<0.05) for meniscus than for articular cartilage. In contrast, the toe region strain, yield strain and failure strain were on average 9.4, 3.1 and 2.3 times greater (p<0.05) for cartilage than for meniscus. There was a significant negative correlation between the strain-dependent tensile moduli of meniscus and articular cartilage samples within the same joints (r=-0.690, p=0.014). In conclusion, the meniscus possesses higher nonlinear and linear elastic stiffness and energy absorption capability before rupture than contacting articular cartilage, while cartilage has longer nonlinear region and can withstand greater strains before failure. These findings point out different load carrying demands that both articular cartilage and meniscus have to fulfil during normal physiological loading activities of knee joints.


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  Kneeling is required during daily living for many patients after total knee replacement (TKR), yet many patients have reported that they cannot kneel due to pain, or avoid kneeling due to discomfort, which critically impacts quality of life and perceived success of the TKR procedure. The objective of this study was to evaluate the effect of component design on patellofemoral (PF) mechanics during a kneeling activity. A computational model to predict natural and implanted PF kinematics and bone strains after kneeling was developed and kinematics were validated with experimental cadaveric studies. PF joint kinematics and patellar bone strains were compared for implants with dome, medialized dome, and anatomic components. Due to the less conforming nature of the designs, change in sagittal plane tilt as a result of kneeling at 90° knee flexion was approximately twice as large for the medialized-dome and dome implants as the natural case or anatomic implant, which may result in additional stretching of the quadriceps. All implanted cases resulted in substantial increases in bone strains compared with the natural knee, but increased strains in different regions. The anatomic patella demonstrated increased strains inferiorly, while the dome and medialized dome showed increases centrally. An understanding of the effect of implant design on patellar mechanics during kneeling may ultimately provide guidance to component designs that reduces the likelihood of knee pain and patellar fracture during kneeling.


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  http://ac.els-cdn.com/S0021929014000232/1-s2.0-S0021929014000232-main.pdf?_tid=76dec3ca-902f-11e7-ab21-00000aab0f02&acdnat=1504392099_3d7b583e66fc35f434dde55a336ef2ed


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  Novel conical beam CT-scanners offer high resolution imaging of knee structures with i.a. contrast media, even under weight bearing. With this new technology, we aimed to determine cartilage strains and meniscal movement in a human knee at 0, 1, 5, and 30min of standing and compare them to the subject-specific 3D finite element (FE) model. The FE model of the volunteer׳s knee, based on the geometry obtained from magnetic resonance images, was created to simulate the creep. The effects of collagen fibril network stiffness, nonfibrillar matrix modulus, permeability and fluid flow boundary conditions on the creep response in cartilage were investigated. In the experiment, 80% of the maximum strain in cartilage developed immediately, after which the cartilage continued to deform slowly until the 30min time point. Cartilage strains and meniscus movement obtained from the FE model matched adequately with the experimentally measured values. Reducing the fibril network stiffness increased the mean strains substantially, while the creep rate was primarily influenced by an increase in the nonfibrillar matrix modulus. Changing the initial permeability and preventing fluid flow through noncontacting surfaces had a negligible effect on cartilage strains. The present results improve understanding of the mechanisms controlling articular cartilage strains and meniscal movements in a knee joint under physiological static loading. Ultimately a validated model could be used as a noninvasive diagnostic tool to locate cartilage areas at risk for degeneration.


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  Deformation of articular cartilage during static loading of a knee joint – Experimental and finite element analysis


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  Indentation testing is widely used to evaluate the mechanical properties of articular cartilage. However, most curve-fitting solutions for indentation analysis require the deformation data of cartilage at the equilibrium state, which often takes the tissue hours to reach. The lengthy testing time reduces the efficiency of indentation, increases the chance of tissue deterioration, and prevents in vivo applications. To overcome these limitations, a novel technique based on principal component analysis (PCA) was developed in this study, which can predict the full indentation creep curve based on the first few minutes' deformation history and the principal components. The accuracy of this technique was confirmed using the indentation data from 40 temporomandibular joint condylar cartilage samples and 17 bovine knee joint samples. The mechanical properties determined by biphasic curve-fitting using predicted and experimental data are in good agreement, with the difference between the two less than 5%. For TMJ and knee cartilages, it is found that any number of full tests beyond eight will not lead to any increase larger than 1% in the accuracy, indicating a low sample number required for prediction. In addition, the principal components of indentation creep curves are consistent for the same type of cartilage tested with identical protocols, but significantly different between two distinct cartilages. Therefore PCA may also represent a new method to compare the mechanical behaviors of different cartilages, as it avoids the assumptions associated with mechanical constitutive models and relies purely on the experimental data.


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  Determine the equilibrium mechanical properties of articular cartilage from the short-term indentation response


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  The aim of this study was to investigate the role of the superficial zone on the mechanical behavior of articular cartilage. Confined compression of articular cartilage was modeled using a biphasic finite element analysis to calculate the one-dimensional deformation of the extracellular matrix (ECM) and movement of the interstitial fluid through the ECM and articular surface. The articular cartilage was modeled as an inhomogeneous, nonlinear hyperelastic biphasic material with depth and strain-dependent material properties. Two loading conditions were simulated, one where the superficial zone was loaded with a porous platen (normal test) and the other where the deep zone was loaded with the porous platen (upside down test). Compressing the intact articular cartilage with 0.2 MPa stress reduced the surface permeability by 88%. Removing the superficial zone increased the rate of change for all mechanical parameters and decreased the fluid support ratio of the tissue, resulting in increased tissue deformation. Apparent permeability linearly increased after superficial removal in the normal test, yet it did not change in the upside down test. Orientation of the specimen affected the time-dependent biomechanical behavior of the articular cartilage, but not equilibrium behavior. The two tests with different specimen orientations resulted in very different apparent permeabilities, suggesting that in an experimental study which quantifies material properties of an inhomogeneous material, the specimen orientation should be stated along with the permeability result. The current study provides new insights into the role of the superficial zone on mechanical behavior of the articular cartilage.


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  A biphasic finite element study on the role of the articular cartilage superficial zone in confined compression


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  Modern fibril-reinforced computational models of articular cartilage can include inhomogeneous tissue composition and structure, and nonlinear mechanical behavior of collagen, proteoglycans and fluid. These models can capture well experimental single step creep and stress-relaxation tests or measurements under small strains in unconfined and confined compression. Yet, it is known that in indentation, especially at high strain velocities, cartilage can express highly nonlinear response. Different fibril reinforced poroelastic and poroviscoelastic models were used to assess measured highly nonlinear stress-relaxation response of rabbit articular cartilage in indentation. Experimentally measured depth-dependent volume fractions of different tissue constituents and their mechanical nonlinearities were taken into account in the models. In particular, the collagen fibril network was modeled using eight separate models that implemented five different constitutive equations to describe the nonlinearity. These consisted of linear elastic, nonlinear viscoelastic and multiple nonlinear elastic representations. The model incorporating the most nonlinearly increasing Young׳s modulus of collagen fibrils as a function of strain captured best the experimental data. Relative difference between the model and experiment was ~3%. Surprisingly, the difference in the peak forces between the experiment and the model with viscoelastic collagen fibrils was almost 20%. Implementation of the measured volume fractions did not improve the ability of the model to capture the measured mechanical data. These results suggest that a highly nonlinear formulation for collagen fibrils is needed to replicate multi-step stress-relaxation response of rabbit articular cartilage in indentation with high strain rates.


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  Highly nonlinear stress-relaxation response of articular cartilage in indentation: Importance of collagen nonlinearity


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  The intricate properties of articular cartilage and the complexity of the loading environment are some of the key challenges in developing models for biomechanical analysis of the knee joint. Fibril-reinforced poroelastic (FRPE) material models have been reported to accurately capture characteristic responses of cartilage during dynamic and static loadings. However, high computational and time costs associated with such advanced models limit applicability of FRPE models when multiple subjects need to be analyzed. If choosing simpler material models, it is important to show that they can still produce truthful predictions. Therefore, the aim of this study was to compare depth-dependent maximum principal stresses and strains within articular cartilage in the 3D knee joint between FRPE material models and simpler isotropic elastic (IE), isotropic poroelastic (IPE) and transversely isotropic poroelastic (TIPE) material models during simulated gait cycle. When cartilage-cartilage contact pressures were matched between the models (15% allowed difference), maximum principal stresses in the IE, IPE and TIPE models were substantially lower than those in the FRPE model (by more than 50%, TIPE model being closest to the FRPE model), and stresses occurred only in compression in the IE model. Additional simulations were performed to find material parameters for the TIPE model (due to its anisotropic nature) that would yield maximum principal stresses similar to the FRPE model. The modified homogeneous TIPE model was in a better agreement with the homogeneous FRPE model, and the average and maximum differences in maximum principal stresses throughout the depth of cartilage were 7% and 9%, respectively, in the lateral compartment and 9% and 11% in the medial compartment. This study revealed that it is possible to match simultaneously maximum principal stresses and strains of cartilage between non-fibril-reinforced and fibril-reinforced knee joint models during gait. Depending on the research question (such as analysis of fibril strain necessitates the use of fibril-reinforced material models) or clinical demand (fast simulations with simpler material models), the choice of the material model should be done carefully.


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  Comparison of different material models of articular cartilage in 3D computational modeling of the knee: Data from the Osteoarthritis Initiative (OAI)


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  Comparison of different material models of articular cartilage in 3D computational modeling of the knee


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  Experimental and theoretical methods were used to investigate the linearity of the stress response of articular cartilage to ramp and sinusoidal tests in confined compression, as well as the role of cartilage-porous platen and lateral confinement boundary conditions in determining material responses. With respect to linearity, we posed the question as to whether the elicited stress responses to ramp compression, ramp release and sinusoidal tests were similar. With respect to boundary conditions we inquired as to the necessity of specifying a detailed interdigitating contact with the porous filter and of specifying the level of confinement present at the lateral edge of the disk. We found that the stress responses to the three types of tests were dissimilar, with ramp compression the only test exhibiting linear behavior. Ramp release from a static compression offset was non-linear in a manner such that the cartilage maintained a compressive stress higher than expected by a linear theory. Sinusoidal compression also displayed a non-linear response consistent with the presence of a release phase in each cycle. The actual boundary conditions present at the cartilage/porous-filter interface were visualized histologically. Areas (tens of microns) of cartilage in contact with the metal of the filter were interspersed with areas expanded into the pores of the filter. Finite-element analysis incorporating this information suggested that precise specification of this interface and of the level of the extent of lateral confinement would be necessary for the estimation of material properties, such as the hydraulic permeability, from these tests. The trends of the linearity studies did not appear to be significantly affected by the problems posed by these difficult to quantitate boundary conditions. The non-linear cartilage response to release and sinusoidal displacements therefore appear to be physiologically interesting. The maintained, that is higher than would be linear, compressive stress observed during release may be a beneficial adaptation to repeated loading where temporal variations in tissue stresses would be minimized.


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  Confined compression of articular cartilage: linearity in ramp and sinusoidal tests and the importance of interdigitation and incomplete confinement


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  https://www.researchgate.net/publication/12822963_Confined_and_unconfined_stress_relaxation_of_cartilage_Appropriateness_of_a_transversely_isotropic_analysis


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  Official Full-Text Paper (PDF): Confined and unconfined stress relaxation of cartilage: Appropriateness of a transversely isotropic analysis


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  Confined and unconfined stress relaxation of cartilage: Appropriateness of a transversely isotropic analysis (PDF Download Available)


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  Previous studies have shown that stress relaxation behavior of calf ulnar growth plate and chondroepiphysis cartilage can be described by a linear transverse isotropic biphasic model. The model provides a good fit to the observed unconfined compression transients when the out-of-plane Poisson's ratio is set to zero. This assumption is based on the observation that the equilibrium stress in the axial direction (deltaz) is the same in confined and unconfined compression, which implies that the radial stress deltar = 0 in confined compression. In our study, we further investigated the ability of the transversely isotropic model to describe confined and unconfined stress relaxation behavior of calf cartilage. A series of confined and unconfined stress relaxation tests were performed on calf articular cartilage (4.5 mm diameter, approximately 3.3 mm height) in a displacement-controlled compression apparatus capable of measuring delta(z) and delta(r). In equilibrium, delta(r) > 0 and delta(z) in confined compression was greater than in unconfined compression. Transient data at each strain were fitted by the linear transversely isotropic biphasic model and the material parameters were estimated. Although the model could provide good fits to the unconfined transients, the estimated parameters overpredicted the measured delta(r). Conversely, if the model was constrained to match equilibrium delta(r), the fits were poor. These findings suggest that the linear transversely isotropic biphasic model could not simultaneously describe the observed stress relaxation and equilibrium behavior of calf cartilage.


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  Confined and unconfined stress relaxation of cartilage: appropriateness of a transversely isotropic analysis


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  An optimized digital image correlation (DIC) technique was applied to investigate the depth-dependent mechanical properties of articular cartilage and simultaneously the depth-dependent nonlinear viscoelastic constitutive model of cartilage was proposed and validated. The creep tests were performed with different stress levels and it is found that the initial strain and instantaneous strain increase; however the creep compliance decreases with the increase of compressive stress. The depth-dependent creep strain of cartilage was obtained by analyzing the images acquired using the optimized DIC technique. Moreover the inhomogeneous creep compliance distributions within the tissues were determined at different creep time points. It is noted that both creep strain and creep compliance with different creep times decrease from cartilage surface to deep. The depth-dependent creep compliance increases with creep time and the increasing amplitude of creep compliance decreases along cartilage depth. The depth-dependent and stress rate dependent nonlinear stress and strain curves were obtained for articular cartilage through uniaxial compression tests. It is found that the Young's modulus of cartilage increases obviously along cartilage depth from superficial layer to deep layer and the Young's modulus of different layers for cartilage increases with the increase of stress rate. The Poisson's ratio of cartilage increases along cartilage depth with given compressive strain and the Poisson's ratio of different layers decreases with the increase of compressive strain. The depth-dependent nonlinear viscoelastic constitutive model was proposed and some creep data were applied to determine the parameters of the model. The depth-dependent compressive behaviors of cartilage were predicted by the model and the results show that there are good agreements between the experimental data and predictions.


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  Depth and rate dependent mechanical behaviors for articular cartilage: experiments and theoretical predictions


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  OBJECTIVE: To investigate the mechanical properties and morphological characteristics of articular cartilage on the tibial plateau of human knees, including the region covered by the meniscus.
  DESIGN: Using a 1-mm diameter flat-ended cylindrical probe to apply a constant load (0.6 MPa) at specific sites on the tibial plateau, the mechanical properties of articular cartilage were studied using seven cadaver knees. Comparison was made between data obtained by the cartilage covered by the meniscus and that not covered. This was done for both the medial and lateral plateaus. Histological sections of the articular cartilage were also performed to study differences between cartilage from these regions of the tibial plateau.
  RESULTS: Compared to cartilage that was not covered by the meniscus, the articular cartilage beneath the meniscus showed a significantly (P<0.05) larger modulus by as much as 70%, and was less thick by about 40%. Also, the subchondral bone quantity and calcified layer thickness were observed to be significantly lesser in the regions covered by the meniscus.
  CONCLUSIONS: Our findings revealed a significant difference between the mechanical properties and associated structures of articular cartilage in the region covered by the meniscus compared with the articular cartilage not covered by the meniscus.


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  OBJECTIVE: To noninvasively assay the mechanical and structural characteristics of articular cartilage from patients with osteoarthritis (OA) by magnetic resonance imaging (MRI), and to further relate spatial patterns of MRI-based mechanical strain to joint (depth-wise, regional) locations and disease severity.
  METHODS: Cylindrical osteochondral explants harvested from human tissue obtained during total knee replacement surgery were loaded in unconfined compression and 2D deformation data was acquired at 14.1 T using a displacements under applied loading by MRI (dualMRI) approach. After imaging, samples were histologically assessed for OA severity. Strains were determined by depth, and statistically analyzed for dependence on region in the joint and OA severity.
  RESULTS: Von Mises, axial, and transverse strains were highly depth-dependent. After accounting for other factors, Von Mises, axial, and shear strains varied significantly by region, with largest strain magnitudes observed in explants harvested from the tibial plateau and anterior condyle near exposed bone. Additionally, in all cases, strains in late-stage OA were significantly greater than either early- or mid-stage OA. Transverse strain in mid-stage OA explants, measured near the articular surface, was significantly higher than early-stage OA explants.
  CONCLUSION: dualMRI was demonstrated in human OA tissue to quantify the effects of depth, joint region, and OA severity, on strains resulting from mechanical compression. These data suggest dualMRI may possess a wide range of utility, such as validating computational models of soft tissue deformation, assaying changes in cartilage function over time, and perhaps, once implemented for cartilage imaging in vivo, as a new paradigm for diagnosis of early- to mid-stage OA.


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  Noninvasive dualMRI-based strains vary by depth and region in human osteoarthritic articular cartilage


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  OBJECTIVE: To explore how changes to the superficial region (SR) of articular cartilage during skeletal development impact its functional properties. It was hypothesised that a functional superficial region is not present in skeletally immature articular cartilage, and removal of this zone of the tissue would only negatively impact the dynamic modulus of the tissue with the attainment of skeletal maturity.
  METHODS: Porcine osteochondral cores were mechanically tested statically and dynamically with and without their respective superficial regions in confined and unconfined compression at different stages of postnatal development and maturation. A novel combination of histological, biochemical and imaging techniques were utilised to accurately describe changes to the superficial region during postnatal development.
  RESULTS: Articular cartilage was found to become stiffer and less permeable with age. The confined and unconfined dynamic modulus significantly decreased after removal of the superficial region in skeletally mature cartilage, whilst no significant change was observed in the 4 week old tissue. Biochemical analysis revealed a significant decrease in overall sGAG content with age (as % dry weight), whilst collagen content significantly increased with age, although the composition of the superficial region relative to the remainder of the tissue did not significantly change with age. Helium ion microscopy (HIM) revealed dramatic changes to the organization of the superficial region with age.
  CONCLUSIONS: The findings demonstrate that the superficial region of articular cartilage undergoes dramatic structural adaptation with age, which in turn plays a key role in determining the dynamic compressive properties of the tissue.


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  The changing role of the superficial region in determining the dynamic compressive properties of articular cartilage during postnatal development


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  Summary To determine if differences in biomechanical properties and biochemical composition exist between human patellar articular cartilage and the opposing femoral articular cartilage. The biomechanical properties and biochemical composition of the articular cartilage of 17 knees from 13 donors were determined for four sites on the patella and three sites on the femur represting regions of contact at 30° and 90° of flexion. The material properties were determined by biphasic indentation testing, yielding the compressive aggregate modulus, HA, permeability, k, and Poisson's ratio, vs. The thickness of the cartilage at the indentation site, h, was also measured using a needle probe. Full-thickness samples of cartilage adjacent to each indentation site were used for wet weight, sulfated glycosaminoglycan content and hydroxyproline content determinations. The patellar cartilage was found to have a lower compressive aggregate modulus by 30% (P<0.001), higher premeability to fluid flow by 66% (P<0.001) and greater thickness by 23% (P=0.017) than that of the opposing femoral cartilage. The Poisson's ratios for both surfaces were found to be nearly zero. The water content of the patella was higher by 5% (P=0.031) and the proteoglycan content lower by 19% (P=0.030) than that of the femur. However, no differences were found between the collagen contents of the cartilages. Significant differences were found between the intrinsic material properties of the patellar cartilage and those of the femoral-trochlear cartilage. This variability of cartilage material properties with the patellofemoral joint may help explain why patellar cartilage has been frequently observed clinically to exhibit earlier and more severe fibrillation changes than the opposing femoral cartilage.


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  Differences in patellofemoral joint cartilage material properties and their significance to the etiology of cartilage surface fibrillation


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  The mechanical properties of articular cartilage vary enormously with loading rate, and how these properties derive from the composition and structure of the tissue is still unclear. This study investigates the mechanical properties of human articular cartilage at rapid rates of loading, compares these with measurements at slow rates of loading and explores how they relate to the gross composition of the tissue. Full-depth femoral head cartilage biopsies were subjected to a slow, unconfined compression test followed by an impact at an energy of 78.5mJ and velocity 1.25ms(-1). The modulus was calculated from the slope of the loading curve and the coefficient of restitution from the areas under the loading and unloading curves. Tissue composition was measured as water, collagen and glycosaminoglycan contents. The maximum dynamic modulus ranged from 25 to 150MPa. These values compared with 1-3MPa measured during quasi-static loading. The coefficient of restitution was 0.502 (0.066) (mean (standard deviation)) and showed no site variation. Water loss was not detectable. Composition was not strongly associated with modulus; water and collagen contents together predicted about 25% of the variance in modulus.


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  The mechanical and material properties of elderly human articular cartilage subject to impact and slow loading


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  https://www.google.com/search?q=Poroelastic+response+of+articular+cartilage+by+nanoindentation+creep+tests+at+different+characteristic+lengths&rlz=1C1CHFX_enUS678US678&oq=Poroelastic+response+of+articular+cartilage+by+nanoindentation+creep+tests+at+different+characteristic+lengths&aqs=chrome..69i57.884j0j4&sourceid=chrome&ie=UTF-8


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  Poroelastic response of articular cartilage by nanoindentation creep tests at different characteristic lengths - Google Search


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  Nanoindentation is an experimental technique which is attracting increasing interests for the mechanical characterization of articular cartilage. In particular, time dependent mechanical responses due to fluid flow through the porous matrix can be quantitatively investigated by nanoindentation experiments at different penetration depths and/or by using different probe sizes. The aim of this paper is to provide a framework for the quantitative interpretation of the poroelastic response of articular cartilage subjected to creep nanoindentation tests. To this purpose, multiload creep tests using spherical indenters have been carried out on saturated samples of mature bovine articular cartilage achieving two main quantitative results. First, the dependence of indentation modulus in the drained state (at equilibrium) on the tip radius: a value of 500 kPa has been found using the large tip (400 μm radius) and of 1.7 MPa using the smaller one (25 μm). Secon, the permeability at microscopic scale was estimated at values ranging from 4.5×10(-16) m(4)/N s to 0.1×10(-16) m(4)/N s, from low to high equivalent deformation. Consistently with a poroelastic behavior, the size-dependent response of the indenter displacement disappears when characteristic size and permeability are accounted for. For comparison purposes, the same protocol was applied to intrinsically viscoelastic homogeneous samples of polydimethylsiloxane (PDMS): both indentation modulus and time response have been found size-independent.


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  Poroelastic response of articular cartilage by nanoindentation creep tests at different characteristic lengths


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  Isotropic hyperelastic models have been used to determine the material properties of normal human cartilage, but there remains an incomplete understanding of how these properties may be altered by osteoarthritis. The aims of this study were to (1) measure the material constants of normal and osteoarthritic human knee cartilage using isotropic hyperelastic models; (2) determine whether the material constants correlate with histological measures of structure and/or cartilage tissue damage; and (3) quantify the abilities of two common isotropic hyperelastic material models, the neo-Hookean and Yeoh models, to describe articular cartilage contact force, area, and pressure. Small osteochondral specimens of normal and osteoarthritic condition were retrieved from human cadaveric knees and from the knees of patients undergoing total knee arthroplasty and tested in unconfined compression at loading rates and large strains representative of weight-bearing activity. Articular surface contact area and lateral deformation were measured concurrently and specimen-specific finite element models then were used to determine the hyperelastic material constants. Structural parameters were measured using histological techniques while the severity of cartilage damage was quantified using the OARSI grading scale. The hyperelastic material constants correlated significantly with OARSI grade, indicating that the mechanical properties of cartilage for large strains change with tissue damage. The measurements of contact area described anisotropy of the tissue constituting the superficial zone. The Yeoh model described contact force and pressure more accurately than the neo-Hookean model, whereas both models under-predicted contact area and poorly described the anisotropy of cartilage within the superficial zone. These results identify the limits by which isotropic hyperelastic material models may be used to describe cartilage contact variables. This study provides novel data for the mechanical properties of normal and osteoarthritic human articular cartilage and enhances our ability to model this tissue using simple isotropic hyperelastic materials.


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  Articular cartilage has pronounced through-the-thickness heterogeneity in both ultrastructure and mechanical function. The tissue undergoes a combination of large deformations in vivo, where shear is critical in both failure and chondrocyte death. Yet the microstructure mechanical response of cartilage to multi-axial large shear deformations is unknown. We harvested a total of 42 cartilage specimens from seven matched locations across the lateral femoral condyles and patellofemoral grooves of six human male donors (30.2±8.8yrs old, M±SD). With each specimen we applied a range of quasi-static, multi-axial large (simple) shear displacements both parallel and perpendicular to the local split-line direction (SLD). Shear stresses in cartilage specimens from the patellofemoral grooves were higher, and more energy was dissipated, at all applied strains under loading parallel to the local SLD versus perpendicular, while specimens from the lateral condyles were mechanically anisotropic only under larger strains of 20% and 25%. Cartilage also showed significant intra-donor variability at larger shear strains but no significant inter-donor variability. Overall, shear strain-energy dissipation was almost constant at 5% applied shear strain and increased nonlinearly with increasing shear magnitude. Our results suggest that full understanding of cartilage mechanics requires large-strain analyses to account for nonlinear, anisotropic and location-dependent effects not fully realized at small strains.


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  Shear deformations of human articular cartilage: Certain mechanical anisotropies apparent at large but not small shear strains


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  Osteoarthritis and articular cartilage injuries are common conditions in human joints and a frequent cause of pain and disability. Unfortunately, cartilage is avascular and has limited capabilities for self-repair. Despite the societal impact, there is little information on the dynamic process of cartilage degeneration. We performed a series of cyclic unconfined compression tests motivated by in vivo loading conditions and designed to generate mechanical fatigue. We examined the functional (both stress-stretch and creep) responses of the tissue after recovery from a specified number of loading cycles, as well as histology and second harmonic generation microscopy images. The effect of compaction was complimented by the effect of fatigue in our unconfined compression tests. A three-way, repeated-measures mixed model ANOVA showed significant differences between loading with a physiologically relevant low magnitude, and two more severe loading magnitudes, in terms of the resulting specimen stiffness, time to equilibrium and thickness. There was a statistically significant effect of loading frequency on a specimen's time to equilibrium and significant interaction of force and frequency on specimen thickness and time to equilibrium. Increasing the number of loading cycles significantly impacted a specimen's effective stiffness and resulting thickness. We attribute permanent loss of mechanical function under cyclic loading to rearrangement and disruption of the collagen network and resulting proteoglycan (PG) aggregation, as seen in histological and second harmonic generation images, as a result of induced mechanical fatigue.


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  Preventing cartilage injury is important in minimizing the long term debilitating effects of osteoarthritis. Accurate subfracture injury prediction must take into account the possible effects that freeze thaw cycles may have on the mechanical properties of cartilage tissue. This paper addresses this concern with matched pair testing of various low temperature storage techniques against fresh control groups. Ten matched pairs of bovine knees were used for testing, five pairs for a -20 degrees C slow freeze cycle and five pairs for a -80 degres C flash freeze cycle. Controlled mechanical indention tests were performed on the bovine articular cartilage-on-bone specimens to compare stiffness, peak stress, and loading energy of the cartilage. Findings showed that a slow freeze cycle or flash freeze cycle caused cartilage stiffness to decrease by 37% and 31% respectively, which was statistically significant in both cases (p< or =0.01). Compressive stress at this strain was also lowered by 31% with a slow freezing process (p=0.03). A similar trend was observed with compressive stress in the flash freeze specimens, although the 37% decrease was not found to be statistically significant (p=0.08). These results may be indicative of a weakened extracellular matrix structure caused by the freeze-thaw process. It is still unclear whether these changes in mechanical properties will result in a change in injury susceptibility for articular cartilage.


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  Articular cartilage function relies on its unique mechanical behavior. Cartilage mechanics have been described by several analytic models, whose parameters are usually estimated by fitting their constitutive equations to stress-relaxation data. This procedure can be long and is prone to experimental and fitting errors. Τhis study describes a novel methodology for estimating the biomechanical properties of cartilage samples based on their linearized frequency response, derived by applying a series of small-amplitude harmonic displacements superimposed to a bias strain. The proposed methodology, denoted as linearized frequency-domain method (LFM), was demonstrated by quantifying the effects of collagenase and hyaluronidase on cartilage, where it provided robust cartilage parameter estimates that overall agreed well with estimates obtained by stress-relaxation analysis. LFM was also applied to unveil the strain-dependent nature of porcine cartilage biomechanical parameters. Results showed that increasing the bias strain from 5% to 15% caused a significant decrease in cartilage permeability but did not have significant effect on the compression modulus and the Poisson's ratio. Apart from cartilage, LFM can potentially quantify the strain-dependent nature of tissues and biomaterials, thereby enhance tissue-level understanding on organ physiology and pathology, lead to better computational tissue models, and guide tissue engineering research.


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  Articular cartilage, which makes possible the painless, low-friction movement of synovial joints, consists of a sparsely distributed population of highly specialized cells called chondrocytes that are embedded within a matrix and provide articular cartilage with remarkable mechanical properties. Chondrocytes form the tissue matrix macromolecular framework from three classes of molecules: collagens, proteoglycans, and noncollagenous proteins. The matrix protects the cells from injury resulting from normal joint use, determines the types and concentrations of molecules that reach the cells, acts as a mechanical signal transducer for the cells, and helps maintain the chondrocyte phenotype. Throughout life, articular cartilage undergoes internal remodeling as the cells replace matrix macromolecules lost through degradation. Aging decreases the ability of chondrocytes to maintain and restore articular cartilage and thereby increases the risk of degeneration of the articular cartilage surface. Progressive degeneration of articular cartilage leads to joint pain and dysfunction that is clinically identified as osteoarthritis. Investigation regarding the pathogenesis of posttraumatic osteoarthritis, the form of osteoarthritis that develops following joint injury, is helping to explain the development and progression of joint degeneration.


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  The relationship between the tensile properties of articular cartilage and age has been investigated in vitro in the human knee joint. Specimens orientated parallel to the articular surface were excised from the superficial and deep zones of the femoral condyles of knee joints of persons in the age range from 8 to 91 years. The results showed that the tensile strength of the superficial zone increased with age to reach a maximum value in the third decade. Thereafter the strength decreased markedly with increasing age. The tensile strength of cartilage from the deep zone did not show an increase in the early years but decreased continuously with age. The tensile stiffness of the superficial layer at stresses of 5 MN/m2 and 10 MN/m2 increased to maximum values in the third decade and thereafter decreased with increasing age. The stiffness of the deep zone decreased continuously with age. It is suggested that these results reflect changes in the organisation of the collagen fibre mesh with age and possibly also changes in the collagen cross-links.


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  As a relatively non-regenerative tissue, articular cartilage has been targeted for cryopreservation as a method of mitigating a lack of donor tissue availability for transplant surgeries. In addition, subzero storage of articular cartilage has long been used in biomedical studies using various storage temperatures. The current investigation studies the potential for freeze-thaw to affect the mechanical properties of articular cartilage through direct comparison of various subzero storage temperatures.


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  https://bmcmusculoskeletdisord.biomedcentral.com/track/pdf/10.1186/1471-2474-11-231?site=bmcmusculoskeletdisord.biomedcentral.com


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  Although the contribution of the circumferential collagen bundles to the anisotropic tensile stiffness of meniscal tissue has been well described, the implications of interactions between tissue components for other mechanical properties have not been as widely examined. This study compared the effects of the proteoglycan-associated osmotic swelling stress on meniscal fibrocartilage and articular cartilage (AC) mechanics by manipulating the osmotic environment and tissue compressive offset. Cylindrical samples were obtained from the menisci and AC of bovine stifles, equilibrated in phosphate-buffered saline solutions ranging from 0.1× to 10×, and tested in oscillatory torsional shear and unconfined compression. Biochemical analysis indicated that treatments and testing did not substantially alter tissue composition. Mechanical testing revealed tissue-specific responses to both increasing compressive offset and decreasing bath salinity. Most notably, reduced salinity dramatically increased the shear modulus of both axially and circumferentially oriented meniscal tissue explants to a much greater extent than for cartilage samples. Combined with previous studies, these findings suggest that meniscal proteoglycans have a distinct structural role, stabilizing, and stiffening the matrix surrounding the primary circumferential collagen bundles.


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  Comparison of osmotic swelling influences on meniscal fibrocartilage and articular cartilage tissue mechanics in compression and shear


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  We measured the in situ biomechanical properties of knee joint cartilage from five species (bovine, canine, human, monkey, and rabbit) to examine the biomechanical relevance of animal models of human knee joint injuries and osteoarthritis. In situ biphasic creep indentation experiments were performed to simultaneously determine all three intrinsic material coefficients (aggregate modulus, Poisson's ratio, and permeability) of the cartilage as represented by the linear KLM biphasic model. In addition, we also assessed the effects of load bearing on these intrinsic properties at "high" and "low" weight-bearing regions on the distal femur. Our results indicate that significant differences exist in some of these material properties among species and sites. The aggregate modulus of the anterior patellar groove within each species is the lowest among all sites tested, and the permeability of the patellar groove cartilage is the highest and does not vary among species. Similarly, the Poison's ratio in the patellar groove is the lowest in all species, except in the rabbit. These results lead to the conclusion that patellar groove cartilage can undergo greater and faster compression. Thus, under high compressive loads, the cartilage of the patellar groove surface can more rapidly compress to create a congruent patellofemoral joint articulation. For any given location, no differences were found in the aggregate modulus among all the species, and no correlation was found between aggregate modulus and thickness at the test site. Thus, in the process of selecting a suitable experimental animal model of human articular cartilage, it is essential to consider the significant interspecies differences of the mechanical properties.


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  The effect of unilateral transection of the anterior cruciate ligament on the confined compression and swelling properties of the distal femoral articular cartilage of skeletally mature rabbits at 9 weeks after surgery was determined. Gross morphological grading of the transected and contralateral control distal femora stained with India ink confirmed that cartilage degeneration had been induced by ligament transection. Osteochondral cores, 1.8 mm in diameter, were harvested from the medial femoral condyles. The modulus, permeability, and electrokinetic (streaming potential) coefficient of the articular cartilage of the osteochondral cores were assessed by confined compression creep experiments. The properties (mean +/- SD) of control cartilage were: confined compression modulus, 0.75 +/- 0.28 MPa; hydraulic permeability, 0.63 +/- 0.28 x 10(-15) m2/Pa*sec; and electrokinetic coefficient, 0.16 +/- 0.31 x 10(-9) V/Pa. In transected knees, the modulus was reduced by 18% (p = 0.04), while the permeability and electrokinetic coefficient were not detectably altered. The change in modulus was accompanied by a trend (p = 0.07) toward a decrease (-11%) in the glycosaminoglycan density within the tissue, a significant increase (p < 0.001) in the water content of the cartilage after equilibration in 1 x phosphate buffered saline from 70.3 +/- 4.1% in control knees to 75.2 +/- 4.0% in transected knees, and little further swelling after tissue equilibration in hypotonic saline. The compressive modulus of the cartilage from both control and transected knees was positively correlated with the density of tissue glycosaminoglycan. The alterations in the physical properties of the articular cartilage after transection of the anterior cruciate ligament in the rabbit show trends similar to those observed in human and other animal models of osteoarthritis and provide further support for the use of this model in the study of cartilage degeneration.


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  Physical properties of rabbit articular cartilage after transection of the anterior cruciate ligament


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  The objective of this study was to determine the equilibrium confined compression modulus of bovine articular cartilage as it varies with depth from the articular surface. Osteochondral samples were compressed by 8, 16, 24, and 32% of the cartilage thickness and allowed to equilibrate. Intratissue displacement within the cartilage was measured with use of fluorescently labeled chondrocyte nuclei as intrinsic, fiducial markers. Axial strain was then calculated in nine sequential 125 microns thick cartilage layers comprising the superficial 1,125 microns and in a 250 microns thick layer of cartilage adjacent to the cartilage-bone interface. Adjacent osteochondral cores were also tested in confined compression to determine the equilibrium stresses required to achieve the same levels of compression. Stress-strain data for each layer of each sample were fit to a finite deformation stress-strain relation to determine the equilibrium confined compression modulus in each tissue layer. The compressive modulus increased significantly with depth from the articular surface and ranged from 0.079 +/- 0.039 MPa in the superficial layer to 1.14 +/- 0.44 MPa in the ninth layer. The deepest layer 250 microns thick, had a modulus of 2.10 +/- 2.69 MPa. These moduli were markedly different from the apparent "homogeneous" modulus for full-thickness cartilage (0.38 +/- 0.12 MPa) and ranged from 21 to 560% of that value. The relatively low moduli and the compression-induced stiffening of the superficial layers suggest that these layers greatly affect the biomechanical behavior of cartilage, such as during confined compression testing. The delineation of the depth-dependent modulus provides a basis for detailed study of the relationship between the composition, structure, and function of cartilage in such processes as aging, repair, and degeneration.


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  Cartilage was obtained from eight matched knee (tibiofemoral and femoropatellar) and ankle (talocrural) joints of five different donors (both left and right from donors 14, 22, and 38 years of age, and left only from donors 31 and 45 years of age) within 24 hours of death. All cartilage was graded as normal by the macroscopic visual Collins' scale and the histological Mankin scale. Cylindrical disks of cartilage were harvested from 10 sites within the tibiofemoral and femoropatellar joint surfaces and four sites within the talocrural joint, and uniaxial confined compression measurements were performed to quantify a spectrum of physical properties including the equilibrium modulus, hydraulic permeability, dynamic stiffness, streaming potential, electrokinetic coupling coefficient, and electrical conductivity. Matched specimens from the same 14 sites were used for complementary measurements of biochemical composition and molecular interaction, including water content, hypotonic swelling behavior, and sulfated glycosaminoglycan and collagen contents. In comparison of the top 1-mm slices of talar cartilage with the top 1-mm of tibiofemoral cartilage, the talar cartilage appeared denser with a higher sulfated glycosaminoglycan content, lower water content, higher equilibrium modulus and dynamic stiffness, and lower hydraulic permeability. The equilibrium modulus increased with increasing sulfated glycosaminoglycans per wet weight and decreased with increasing water content for all joint surfaces. Multiple linear regression showed that greater than 80% of the variation in the equilibrium modulus could be accounted for by variations in the biochemical parameters (water content, sulfated glycosaminoglycans/wet weight, and hydroxyproline content/wet weight) for each joint surface. Nonhomogeneous depth-dependent changes in the physical properties and biochemical composition of full-thickness distal femoral cartilage were consistent with previous reports. Since the compressive deformation of cartilage during cyclic loading is confined to the more superficial regions, the differences in properties of the upper regions of the talar compared with tibiofemoral or femoropatellar cartilage may be important in the etiology of osteoarthritis.


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  Mechanical behavior of bone is determined by the structure and intrinsic, local material properties of the tissue. However, previously presented knee joint models for evaluation of stresses and strains in joints generally consider bones as rigid bodies or linearly elastic solid materials. The aim of this study was to estimate how different structural and mechanical properties of bone affect the mechanical response of articular cartilage within a knee joint. Based on a cadaver knee joint, a two-dimensional (2D) finite element (FE) model of a knee joint including bone, cartilage, and meniscus geometries was constructed. Six different computational models with varying properties for cortical, trabecular, and subchondral bone were created, while the biphasic fibril-reinforced properties of cartilage and menisci were kept unaltered. The simplest model included rigid bones, while the most complex model included specific mechanical properties for different bone structures and anatomically accurate trabecular structure. Models with different porosities of trabecular bone were also constructed. All models were exposed to axial loading of 1.9 times body weight within 0.2 s (mimicking typical maximum knee joint forces during gait) while free varus-valgus rotation was allowed and all other rotations and translations were fixed. As compared to results obtained with the rigid bone model, stresses, strains, and pore pressures observed in cartilage decreased depending on the implemented properties of trabecular bone. Greatest changes in these parameters (up to -51% in maximum principal stresses) were observed when the lowest modulus for trabecular bone (measured at the structural level) was used. By increasing the trabecular bone porosity, stresses and strains were reduced substantially in the lateral tibial cartilage, while they remained relatively constant in the medial tibial plateau. The present results highlight the importance of long bones, in particular, their mechanical properties and porosity, in altering and redistributing forces transmitted through the knee joint.


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  Importance of material properties and porosity of bone on mechanical response of articular cartilage in human knee joint--a two-dimensional finite element study


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  Descriptions of the mechanical behaviors of articular cartilage and their correlations with collagen, proteoglycan, water, and ions are summarized, with particular emphasis on understanding the osmotic effect inside the tissue. First, a descriptive explanation is presented of the biphasic theory required to understand how interstitial water contributes toward the viscoelastic behavior of any hydrated soft tissue. Then, the famous osmotic effect in charged, hydrated soft tissue is interpreted in light of the triphasic mixture theory framework. In the introduction of mechanical testing methods, our emphasis is on the popular indentation technique, which can determine the material properties of cartilage in situ or in vivo. The widely accepted indentation analysis solutions in cartilage biomechanics history are summarized and evaluated. At the end of this paper, a new generalized correspondence principle between charged, hydrated soft tissue and linear, isotropic, elastic material (i.e., elasticity theory) is introduced. This principle makes the employment of triphasic theory as straightforward as using an elasticity theory to solve any equilibrium problem where the elasticity theory can be used to model the material. By using this generalized correspondence principle, the fixed charge density of bovine cartilage has been simply and conveniently calculated from the indentation testing data. The results of proteoglycan content from this mechanical test are remarkably consistent with those from standard biochemical assay. This new correspondence principle significantly improves the power of indentation tests in the determination of mechanoelectrochemical properties of articular cartilage.


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  The axial and radial compressive moduli of the human meniscus are important material properties in tibiofemoral joint models, but they have not been determined previously for fresh-frozen tissue. Our goals were to measure the moduli at equilibrium and at a physiological strain rate, to determine whether the axial and radial compressive moduli are equal for each type of loading, and to determine whether they depend on the region (i.e., anterior, middle, posterior) of the meniscus. Samples from each region from 10 fresh-frozen human medial menisci were tested in unconfined compression at four strain levels (3%, 6%, 9%, and 12%) at 32%/s, a strain rate determined to be physiologically relevant to walking, and then allowed to reach equilibrium in stress relaxation. At equilibrium, the axial and radial compressive moduli at 12% strain were 83.4 kPa and 76.1 kPa, respectively (p = 0.58), whereas at the physiological strain rate, the axial and radial compressive moduli at 12% strain were 718 kPa and 605 kPa, respectively (p = 0.61). At the physiological strain rate, the modulus increased with increasing strain (79.2 kPa at 3% strain vs. 662 kPa at 12% strain) and the modulus in the anterior region (1,048 kPa at 12% strain) was significantly greater than that in the posterior region (329 kPa at 12% strain) (p = 0.04). Our study supports a plane of isotropy for the material properties of meniscal tissue. However, the material behavior is strongly nonlinear because the compressive modulus is several orders of magnitude smaller than previously reported values for tensile modulus. Further, the compressive modulus depends on the activity of interest (i.e., static such as standing or dynamic such as walking) due to viscoelastic effects, the strain level, and the region of the tissue.


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  Compressive moduli of the human medial meniscus in the axial and radial directions at equilibrium and at a physiological strain rate


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  http://ac.els-cdn.com/S0011224013001089/1-s2.0-S0011224013001089-main.pdf?_tid=6cd6ca14-9032-11e7-a69d-00000aacb35e&acdnat=1504393370_31e35c408aa9f1fdff8216c7e77b0774


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  Tensile stiffness of articular cartilage is much greater than its compressive stiffness and plays an essential role even in compressive properties by increasing transient fluid pressures during physiological loading. Recent studies of nonlinear properties of articular cartilage in compression revealed several physiologically pertinent nonlinear behaviors, all of which required that cartilage tensile stiffness increase significantly with stretch. We therefore performed sequences of uniaxial tension tests on fresh bovine articular cartilage slices using a protocol that allowed several hours to attain equilibrium and measured longitudinal and transverse tissue strain. By testing bovine cartilage from different ages (6 months to 6 years) we found that equilibrium and transient tensile modulus increased significantly with maturation and age, from 0 to 15 MPa at equilibrium and from 10 to 28 MPa transiently. Our results indicate that cartilage stiffens with age in a manner similar to other highly hydrated connective tissues, possibly due to age-dependent content of enzymatic and nonenzymatic collagen cross links. The long relaxation period used in our tests (5-10 hours) was necessary in order to attain equilibrium and avoid a very significant overestimation of equilibrium modulus that occurs when much shorter times are used (15-30 minutes). We also found that equilibrium and transient tensile modulus increased nonlinearly when cartilage is stretched from 0 to 10% strain without any previous tare load. Although our results estimate a nonlinear increase in tensile stiffness with stretch that is an order of magnitude lower than that required to predict nonlinear properties in compression, they are in agreement with previous results from other uniaxial tension tests of collagenous materials. We therefore speculate that biaxial tensile moduli may be much higher and thereby more compatible with observed nonlinear compressive properties.


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  Articular cartilages and menisci are generally considered to be elastic in the published human knee models, and thus the fluid-flow dependent response of the knee has not been explored using finite element analysis. In the present study, the fluid pressure and site-specific collagen fiber orientation in the cartilages and menisci were implemented into a finite element model of the knee using fibril-reinforced modeling previously proposed for articular cartilage. The geometry of the knee was obtained from magnetic resonance imaging of a healthy young male. The bones were considered to be elastic due to their greater stiffness compared to that of the cartilages and menisci. The displacements obtained for fast ramp compression were essentially same as those for instantaneous compression of equal magnitude with the fluid being trapped in the tissues, which was expected. However, a clearly different pattern of displacements was predicted by an elastic model using a greater Young's modulus and a Poisson's ratio for nearly incompressible material. The results indicated the influence of fluid pressure and fiber orientation on the deformation of articular cartilage in the knee. The fluid pressurization in the femoral cartilage was somehow affected by the site-specific fiber directions. The peak fluid pressure in the femoral condyles was reduced by three quarters when no fibril reinforcement was assumed. The present study indicates the necessity of implementing the fluid pressure and anisotropic fibril reinforcement in articular cartilage for a more accurate understanding of the mechanics of the knee.


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  Aims of the present study were to test the hypotheses that (1) the compressive properties of articular cartilage are affected more by changes in the medium ionic concentration than the tensile properties, (2) collagen network controls the compression–tension nonlinearity of articular cartilage, and (3) proteoglycan (PG) and collagen contents are primary determinants of the compressive and tensile properties of cartilage, respectively. These hypotheses were experimentally tested by axial compressive and tensile tests (perpendicular to the cartilage surface) of bovine articular cartilage samples immersed in 0.005M (n=6), 0.15M (n=12) and 1.0M (n=6) saline solutions. Compressive and tensile behaviour was analyzed by a nonlinear fibril-reinforced poroelastic model. Tissue PG and collagen contents were measured using Fourier transform infrared imaging spectroscopy (FT-IRIS). The compressive modulus of cartilage varied significantly (n=6, p<0.05) as the medium concentration changed. The tensile modulus changed significantly only as the medium concentration was reduced from 0.15 to 0.005M (n=6, p<0.05). The fibril-reinforced poroelastic model with stiff, nonlinear collagen fibrils predicted the experimentally measured compression–tension nonlinearity of cartilage. Tissue PG and collagen contents accounted for the compressive and tensile properties of cartilage.


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  Compressive and tensile properties of articular cartilage in axial loading are modulated differently by osmotic environment


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  Knowledge of the extent to which tibial plateau cartilage displays non-uniform mechanical topography under physiologically relevant loading conditions is critical to evaluating the role of biomechanics in knee osteoarthritis. Cartilage explants from 21 tibial plateau sites of eight non-osteoarthritic female cadaveric knees (age: 41-54; BMI: 14-20) were tested in unconfined compression at 100% strain/s. The elastic tangent modulus at 10% strain (E(10%) ) was calculated for each site and averaged over four geographic regions: not covered by meniscus (I); covered by meniscus-anterior (II); covered by meniscus-exterior (III); and covered by meniscus-posterior (IV). A repeated-measures mixed model analysis of variance was used to test for effects of plateau, region, and their interaction on E(10%) . Effect sizes were calculated for each region pair. E(10%) was significantly different (p<0.05) for all regional comparisons, except I-II and III-IV. The regional pattern of variation was consistent across individuals. Moderate to strong effect sizes were evident for regional comparisons other than I-II on the lateral side and III-IV on both sides. Healthy tibial cartilage exhibits significant mechanical heterogeneity that manifests in a common regional pattern across individuals. These findings provide a foundation for evaluating the biomechanical mechanisms of knee osteoarthritis.


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  Articular cartilage has well known depth-dependent structure and has recently been shown to have similarly non-uniform depth-dependent mechanical properties. Here, we study anatomic variation of the depth-dependent shear modulus and energy dissipation rate in neonatal bovine knees. The regions we specifically focus on are the patellofemoral groove, trochlea, femoral condyle, and tibial plateau. In every sample, we find a highly compliant region within the first 500 µm of tissue measured from the articular surface, where the local shear modulus is reduced by up to two orders of magnitude. Comparing measurements taken from different anatomic sites, we find statistically significant differences localized within the first 50 µm. Histological images reveal these anatomic variations are associated with differences in collagen density and fiber organization.


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  The knowledge of articular cartilage contact biomechanics in the knee joint is important for understanding the joint function and cartilage pathology. However, the in vivo tibiofemoral articular cartilage contact biomechanics during gait remains unknown. The objective of this study was to determine the in vivo tibiofemoral cartilage contact biomechanics during the stance phase of treadmill gait. Eight healthy knees were magnetic resonance (MR) scanned and imaged with a dual fluoroscopic system during gait on a treadmill. The tibia, femur and associated cartilage were constructed from the MR images and combined with the dual fluoroscopic images to determine in vivo cartilage contact deformation during the stance phase of gait. Throughout the stance phase of gait, the magnitude of peak compartmental contact deformation ranged between 7% and 23% of the resting cartilage thickness and occurred at regions with thicker cartilage. Its excursions in the anteroposterior direction were greater in the medial tibiofemoral compartment as compared to those in the lateral compartment. The contact areas throughout the stance phase were greater in the medial compartment than in the lateral compartment. The information on in vivo tibiofemoral cartilage contact biomechanics during gait could be used to provide physiological boundaries for in vitro testing of cartilage. Also, the data on location and magnitude of deformation among non-diseased knees during gait could identify where loading and later injury might occur in diseased knees.


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  Successful treatment of the injured knee depends on a fundamental understanding of the anatomy andbiomechanical function of the structures that comprise the knee. The major structures of the knee are presented anatomically, followed by a brief review of the biomechanics of each. Normal function, as well as the expected result of injury is presented. This review is intended to assist in clinical diagnosis, as well as treatment planning for the injured knee.


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  The mechanical characteristics of biological materials underpin proper joint function. Changes to these structures through repair or replacement without appreciating the underlying structure–function relationships are likely to alter joint kinematics and predispose the joint to osteoarthritis and other degenerative changes. This paper will review the mechanical characteristics of bone, cartilage, the menisci, tendons and ligaments. In-depth knowledge of the mechanical behaviour of these structures is essential for replicating their mechanical function, but also provides a means to identify the perhaps still unappreciated function of many tissues. The paper aims to instil a general appreciation for all tissues of the human joints, hoping that future surgeons will proceed with caution and understanding when repairing or replacing tissue.


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  Osteoarthritis is the most common joint disease and a major cause of disability. The knee is the large joint most affected. While chronological age is the single most important risk factor of osteoarthritis, the pathogenesis of knee osteoarthritis in the young patient is predominantly related to an unfavorable biomechanical environment at the joint. This results in mechanical demand that exceeds the ability of a joint to repair and maintain itself, predisposing the articular cartilage to premature degeneration. This review examines the available basic science, preclinical and clinical evidence regarding several such unfavorable biomechanical conditions about the knee: malalignment, loss of meniscal tissue, cartilage defects and joint instability or laxity. Level of evidence IV.


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  The aim of this study was to investigate the associations between the properties of the cartilage matrix and the results of T2 mapping and delayed gadolinium-enhanced magnetic resonance imaging (dGEMRIC) in human knee osteoarthritic cartilage. Osteochondral samples were harvested from the middle part of the femoral condyle and tibial plateaus of 20 patients with knee osteoarthritis (OA) during total knee arthroplasty. Sagittal T2 mapping, T1pre, and T1Gd were performed using 7.0T magnetic resonance imaging (MRI). Glycosaminoglycan (GAG) distribution was evaluated by OARSI, collagen anisotropy was assessed by polarized light microscopy (PLM), and biochemical analyses measured water, GAG, and collagen content. Associations between properties of the cartilage matrix and T2 and ΔR1 (1/T1Gd-1/T1pre) values were explored using correlation analysis. T2 and ΔR1 values were significantly correlated with the degree of cartilage degeneration (OARSI grade; Ρ = 0.53 and 0.77). T2 values were significantly correlated with water content (r = 0.69; P < 0.001), GAG content (r = -0.43; P < 0.001), and PLM grade (r = 0.47; P < 0.001), but not with collagen content (r = -0.02; P = 0.110). ΔR1 values were significantly correlated with GAG content (r = -0.84; P < 0.001) and PLM grade (r = 0.41; P < 0.001). Taken together, T2 mapping and dGEMRIC results were correlated with the properties of the cartilage matrix in human knee osteoarthritic cartilage. Combination T2 mapping and dGEMRIC represents a potential non-invasive monitoring technique to detect the progress of knee OA.


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  Associations between the properties of the cartilage matrix and findings from quantitative MRI in human osteoarthritic cartilage of the knee


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  Computational mechanics has been advanced in every area of orthopedic biomechanics. The objective of this paper is to provide a general review of the computational models used in the analysis of the mechanical function of the knee joint in different loading and pathological conditions. Major review articles published in related areas are summarized first. The constitutive models for soft tissues of the knee are briefly discussed to facilitate understanding the joint modeling. A detailed review of the tibiofemoral joint models is presented thereafter. The geometry reconstruction procedures as well as some critical issues in finite element modeling are also discussed. Computational modeling can be a reliable and effective method for the study of mechanical behavior of the knee joint, if the model is constructed correctly. Single-phase material models have been used to predict the instantaneous load response for the healthy knees and repaired joints, such as total and partial meniscectomies, ACL and PCL reconstructions, and joint replacements. Recently, poromechanical models accounting for fluid pressurization in soft tissues have been proposed to study the viscoelastic response of the healthy and impaired knee joints. While the constitutive modeling has been considerably advanced at the tissue level, many challenges still exist in applying a good material model to three-dimensional joint simulations. A complete model validation at the joint level seems impossible presently, because only simple data can be obtained experimentally. Therefore, model validation may be concentrated on the constitutive laws using multiple mechanical tests of the tissues. Extensive model verifications at the joint level are still crucial for the accuracy of the modeling.


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  At mechanical equilibrium, articular cartilage is usually characterized as an isotropic elastic material with no interstitial fluid flow. In this study, the equilibrium properties (Young's modulus, aggregate modulus and Poisson's ratio) of bovine humeral, patellar and femoral cartilage specimens (n=26) were investigated using unconfined compression, confined compression, and indentation tests. Optical measurements of the Poisson's ratio of cartilage were also carried out. Mean values of the Young's modulus (assessed from the unconfined compression test) were 0.80±0.33, 0.57±0.17 and 0.31±0.18MPa and of the Poisson's ratio (assessed from the optical test) 0.15±0.06, 0.16±0.05 and 0.21±0.05 for humeral, patellar, and femoral cartilages, respectively. The indentation tests showed 30–79% (p<0.01) higher Young's modulus values than the unconfined compression tests. In indentation, values of the Young's modulus were independent of the indenter diameter only in the humeral cartilage. The mean values of the Poisson's ratio, obtained indirectly using the mathematical relation between the Young's modulus and the aggregate modulus in isotropic material, were 0.16±0.06, 0.21±0.05, and 0.26±0.08 for humeral, patellar, and femoral cartilages, respectively. We conclude that the values of the elastic parameters of the cartilage are dependent on the measurement technique in use. Based on the similar values of Poisson's ratios, as determined directly or indirectly, the equilibrium response of articular cartilage under unconfined and confined compression is satisfactorily described by the isotropic elastic model. However, values of the isotropic Young's modulus obtained from the in situ indentation tests are higher than those obtained from the in vitro unconfined or confined compression tests and may depend on the indenter size in use.


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  Comparison of the equilibrium response of articular cartilage in unconfined compression, confined compression and indentation


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  Articular cartilage exhibits anisotropic mechanical properties when subjected to tension. However, mechanical anisotropy of mature cartilage in compression is poorly known. In this study, both confined and unconfined compression tests of cylindrical cartilage discs, taken from the adult human patello-femoral groove and cut either perpendicular (normal disc) or parallel (tangential disc) to the articular surface, were utilized to determine possible anisotropy in Young's modulus, E, aggregate modulus, Ha, Poisson's ratio, v and hydraulic permeability, k, of articular cartilage. The results indicated that Ha was significantly higher in the direction parallel to the articular surface as compared with the direction perpendicular to the surface (Ha = 1.237 +/- 0.486 MPa versus Ha = 0.845 +/- 0.383 MPa, p = 0.017, n = 10). The values of Poisson's ratio were similar, 0.158 +/- 0.148 for normal discs compared with 0.180 +/- 0.046 for tangential discs. Analysis using the linear biphasic model revealed that the decrease of permeability during the offset compression of 0-20 per cent was higher (p = 0.015, n = 10) in normal (from 25.5 x 10(-15) to 1.8 x 10(-15) m4/N s) than in tangential (from 12.3 x 10(-15) to 1.3 x 10(-15) m4/N s) discs. Based on the results, it is concluded that the mechanical characteristics of adult femoral groove articular cartilage are anisotropic also during compression. Anisotropy during compression may be essential for normal cartilage function. This property has to be considered when developing advanced theoretical models for cartilage biomechanics.


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  In vitro electromechanical and biomechanical testing of articular cartilage provide critical information about the structure and function of this tissue. Difficulties obtaining fresh tissue and lengthy experimental testing procedures often necessitate a storage protocol, which may adversely affect the functional properties of cartilage. The effects of storage at either 4°C for periods of 6 days and 12 days, or during a single freeze-thaw cycle at -20°C were examined in young bovine cartilage. Non-destructive electromechanical measurements and unconfined compression testing on 3 mm diameter disks were used to assess cartilage properties, including the streaming potential integral (SPI), fibril modulus (Ef), matrix modulus (Em), and permeability (k). Cartilage disks were also examined histologically. Compared with controls, significant decreases in SPI (to 32.3±5.5% of control values, p<0.001), Ef (to 31.3±41.3% [corrected] of control values, p=0.046), Em (to 6.4±8.5% of control values, p<0.0001), and an increase in k (to 2676.7±2562.0% of control values, p=0.004) were observed at day 12 of refrigeration at 4°C, but no significant changes were detected at day 6. A trend toward detecting a decrease in SPI (to 94.2±6.2% of control values, p=0.083) was identified following a single freeze-thaw cycle, but no detectable changes were observed for any biomechanical parameters. All numbers are mean±95% confidence interval. These results indicate that fresh cartilage can be stored in a humid chamber at 4°C for a maximum of 6 days with no detrimental effects to cartilage electromechanical and biomechanical properties, while one freeze-thaw cycle produces minimal deterioration of biomechanical and electromechanical properties. A comparison to literature suggested that particular attention should be paid to the manner in which specimens are thawed after freezing, specifically by minimizing thawing time at higher temperatures.


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  Effects of refrigeration and freezing on the electromechanical and biomechanical properties of articular cartilage


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  OBJECTIVE: To examine the functional behavior of the surface layer of the meniscus by investigating depth-varying compressive strains during unconfined compression.
  DESIGN: Pairs of meniscus and articular cartilage explants (n=12) site-matched at the tibial surfaces were subjected to equilibrium unconfined compression at 5, 10, 15, and 20% compression under fluorescence imaging. Two-dimensional (2D) deformations were tracked using digital image correlation (DIC). For each specimen, local compressive engineering strains were determined in 200 μm layers through the depth of the tissue. In samples with sharp strain transitions, bilinear regressions were used to characterize the surface and interior tissue compressive responses.
  RESULTS: Meniscus and cartilage exhibited distinct depth-dependent strain profiles during unconfined compression. All cartilage explants had elevated compressive engineering strains near the surface, consistent with previous reports. In contrast, half of the meniscus explants tested had substantially stiffer surface layers, as indicated by surface engineering strains that were ∼20% of the applied compression. In the remaining samples, surface and interior engineering strains were comparable. 2D Green's strain maps revealed highly heterogeneous compressive and shear strains throughout the meniscus explants. In cartilage, the maximum shear strain appeared to be localized at 100-250 μm beneath the articular surface.
  CONCLUSIONS: Meniscus was characterized by highly heterogeneous strains during compression. In contrast to cartilage, which consistently had a compliant surface region, meniscal explants were either substantially stiffer near the surface or had comparable compressive stiffness through the depth. The relatively compliant interior may allow the meniscus to maintain a consistent surface contour while deforming during physiologic loading.


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  Meniscus and cartilage exhibit distinct intra-tissue strain distributions under unconfined compression


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  Computational analyses have been used to study the biomechanical microenvironment of the chondrocyte that cannot be assessed by in vitro experimental studies; yet all computational studies thus far have focused on the effect of zonal location (superficial, middle, and deep) on the mechanical microenvironment of chondrocytes. The aim of this paper was to study the effect of both zonal and radial locations on the biomechanical microenvironment of chondrocytes in inhomogeneous cartilage under unconfined stress relaxation. A biphasic multiscale approach was employed and nine chondrocytes in different locations were studied. Hyperelastic biphasic theory and depth-dependent aggregate modulus and permeability of articular cartilage were included in the models. It was found that both zonal and radial locations affected the biomechanical stresses and strains of the chondrocytes. Chondrocytes in the mid-radial location had increased volume during the early stage of the loading process. Maximum principal shear stress at the interface between the chondrocyte and the extracellular matrix (ECM) increased with depth, yet that at the ECM-pericellular matrix (PCM) interface had an inverse trend. Fluid pressure decreased with depth, while the fluid pressure difference between the top and bottom boundaries of the microscale model increased with depth. Regardless of location, fluid was exchanged between the chondrocyte, PCM, and ECM. These findings suggested that even under simple compressive loading conditions, the biomechanical microenvironment of the chondrocytes, PCM and ECM was spatially dependent. The current study provides new insight on chondrocyte biomechanics.


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  A biphasic multiscale study of the mechanical microenvironment of chondrocytes within articular cartilage under unconfined compression


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  https://www.google.com/search?q=A+biphasic+finite+element+study+on+the+role+of+the+articular+cartilage+superficial+zone+in+confined+compression&rlz=1C1CHFX_enUS678US678&oq=A+biphasic+finite+element+study+on+the+role+of+the+articular+cartilage+superficial+zone+in+confined+compression&aqs=chrome..69i57j69i60j69i64l3.334j0j4&sourceid=chrome&ie=UTF-8


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  A biphasic finite element study on the role of the articular cartilage superficial zone in confined compression - Google Search


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  METHODS: The instantaneous compressive modulus of articular cartilage was surveyed in 11 sets of human lower limb joints obtained from the ipsilateral side. The average modulus for the entire joint surface of each joint and the topographical variations in the modulus within each joint were examined for all 11 sets, and subjected to statistical analysis.
  RESULTS: Within each set of joints (hip, knee and ankle), the ankle always had a significantly greater mean compressive modulus than the hip and knee (P < 0.001-P < 0.05). In seven sets of joints, there was no significant difference between the mean compressive moduli of the knee and hip joints. In three sets of joints, the compressive modulus of the knee was significantly greater than that of the hip (P < 0.001-P < 0.01), while in only one set of joints was the compressive modulus of the hip significantly greater than that of the knee (P < 0.01).
  CONCLUSION: The topographical variations in the cartilage instantaneous compressive modulus over the surfaces of the lower limb joints were matched by differences in the stresses occurring in different areas of each joint. The results of the present study corroborate previous findings and show that the site-specific stresses and corresponding values of the instantaneous cartilage compressive modulus over the surfaces of lower limb joints were correlated (r = 0.82 at P < 0.01), thus adding credence to the conditioning hypothesis of cartilage by prevalent stress.


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  There is a wealth of data published on the biomechanical properties of intra-articular tissues. However, much of this information is not intuitively applicable to clinical practice due to both methodological disparity between studies and the relevance of the methodology used to test the biomaterial. This inevitably results in comparison difficulties with other experimental data produced for the same tissue, or indeed different tissues. Therefore, this review highlights the salient issues that need to be considered when trying to interpret biomechanical testing scenarios and how they influence clinical practice. As such, different testing protocols and their clinical relevance are scrutinised. The importance of recreating the physiological loading conditions and the interpretation of the functional anatomy are highlighted.


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  Mechanical loading plays an important role not solely in cartilage development, but also in cartilage degeneration. Its adaptation behavior to mechanical loading has not been clearly delineated. The aim of the study was to examine the effect of different running modes (with different muscle contraction types) on morphological, biochemical, and mechanical properties of articular cartilage in the knee of growing rats. Thirty-six female Sprague-Dawley rats were randomly assigned into a nonactive age-matched control (AMC), level (LEVEL), and 20° downhill (DOWN) running group (n = 12 each). Running groups were trained on a treadmill for 30 min/day, 5 days/week for 6 weeks. Immunohistochemical staining and analysis of expression for collagen II, collagen IX, cartilage oligomeric matrix protein (COMP), and matrilin-3, histomorphometry of femoral cartilage height and femoral COMP staining height, and indentation testing of tibial articular cartilage were performed. Rats subjected to downhill running showed a significantly (P = 0.015) higher COMP staining height and a tendentially (P = 0.084) higher cartilage height in the high-weight bearing area of femoral articular cartilage. Cartilage thickness, mechanical properties, and expression of cartilage network proteins in tibial cartilage remained unaffected by different running modes. Our data suggest that joint loading induced by eccentric muscle contractions during downhill running may lead to a site-specific adaptation.


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  Effect of different running modes on the morphological, biochemical, and mechanical properties of articular cartilage


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  Previous decades of cartilage research have predominantly focused on decoupling the solid and fluid interactions of the mechanical response.  The resulting biphasic and triphasic models are widely used in the biomechanics community.  However, a simple viscoelastic model is able to account for the stress-relaxation behavior of cartilage, without the added complexity of solid and fluid interactions.  Using a viscoelastic model, cartilage is considered a single material with elastic and dissipative properties.  A mechanical characterization is made with fewer material parameters than are required by the conventional biphasic and triphasic models.  This approach has tremendous utility when comparing cartilage of different species and varying healths.  Additionally, the viscoelastic models can be easily extended in dynamic analysis and FEA programs.

  Cartilage primarily experiences compressive motion during exercise.  Therefore, to mimic biological function, a mechanical test should also compress the cartilage.  One such test is a viscoelastic stress-relaxation experiment.  The Prony and fractional calculus viscoelastic models have shown promise in modeling stress-relaxation of equine articular cartilage.  The elastic-viscoelastic correspondence principle is used to extend linear viscoelasticity to the frequency domain.  This provides a comparison of articular cartilage based on stored and dissipated moduli.  The storage and loss moduli metrics are hypothesized to serve as benchmarks for evaluating osteoarthritic cartilage, and provide guidelines for newly engineered bio-materials.

  The main goal of the current study is to test the applicability of modeling articular cartilage with viscoelastic models.  A secondary goal is to establish a rigorous set of harvesting techniques that allows access to fresh explants with minimal environmental exposure.  With a complex substance like cartilage, it is crucial to avoid unnecessary emph{in vitro} environmental exposure.  Additional areas of study include: determining the strain-dependency of the mechanical response, exploring the response of cartilage in different fluid mediums such as saline, synovial fluid, and synthetic substitutes, and studying the time-dependent properties of cartilage during stress-relaxation experiments.  Equine stifle joints, which are mechanically analogous to human knees, are harvested and used for analysis in this study.  It is believed that the proposed viscoelastic models can model other articulating joints as well.  If viscoelastic theory can be used to characterize cartilage, then comparisons can be drawn between real and artificial cartilage, leading to better joint replacement technology.


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  Implanted cartilage replacements (ICRs) are a promising approach to restore the functionality of joints with partial- and full-thickness articular cartilage lesions. Two major hurdles hindering successful repair of cartilage injuries with ICRs are their inadequate mechanical properties and fixation into the defect area. While the ICR geometry and mechanical properties are expected to affect the loads and deformations at the adhesive interface between the implant and native cartilage, little is known about the relationship between these implant characteristics and the quality of the fixation. The objective of this study was to evaluate the effect of implant size, thickness, modulus, surface coefficient of friction and Poisson's ratio on the failure of a fibrin adhesive interface. These factors were evaluated in an idealized finite element model of the medial compartment of the human knee with the damage and failure of fibrin at the implant/cartilage interface represented by a cohesive zone model. Both axial compression and sliding were included in the loading conditions. The results demonstrated that ICR size and material properties have a significant effect on the failure of the fibrin that adheres the implant to the native tissue. Lack of anchorage to underlying bone, larger implant sizes, higher surface coefficient of friction and higher compliance of the implant can increase the chance of implant loosening and delamination. In the future, these results may guide implant design and cartilage repair techniques.


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  Implant size and mechanical properties influence the failure of the adhesive bond between cartilage implants and native tissue in a finite element analysis


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  INTRODUCTION: Although fatigue has been implicated in cartilage failure, there are only two published studies in this area, by the same author. However, in these previous studies cartilage was tested in the direction parallel to that of collagen orientation in the superficial layer, where it possesses greater tensile strength. In the present work, articular cartilage was also tested along the direction perpendicular to that of the collagen. Furthermore, the study investigated topographic and zonal variations in the fatigue behaviour of cartilage from the human knee.
  METHODS: Specimens were tested in a specially constructed apparatus that allowed the number of cycles at specimen failure, as well as the load and elongation of the specimen, to be monitored for each specimen. To date, some 72 specimens have been tested, all from the same knee joint, though from different sites and at different depths within the cartilage layer.
  RESULTS AND CONCLUSIONS: The most impressive of the outcomes of this study is the scatter of the data. Considering all the specimens used, the range of number of load cycles to failure was between 2 and 1.5 million. The zonal variation in fatigue behaviour was similar to that in tensile modulus reported previously; the surface and deep layers seemed to have better fatigue properties whether tested in the direction parallel or perpendicular to that of the collagen in the superficial layer. The middle layer was far weaker, suggesting that highly packed and ordered fibres in the surface and deep zones have better mechanical properties than the more random and loose fibres in the middle zone. The variation in fibre organization through the cartilage thickness was also reflected in the differences observed in the elongation of the specimen during the test. The surface and deep zones had a higher stiffness than the middle zone. Cartilage had better fatigue resistance when the specimen was loaded in a direction parallel rather than perpendicular to the collagen within the surface layer. This was true whether specimens were harvested from the superficial, intermediate or deep layer. There were many factors that confounded attempts to estimate the likely fatigue life from the data obtained in such a study.


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  In a series of 103 specimens from the lateral facet of the human patella, the intrinsic mechanical properties of articular cartilage were measured using a confined compression creep test. By considering the cartilage as a porous, permeable solid filed with fluid, this experimental procedure allowed the determination of the intrinsic equilibrium modulus of the cartilage matrix and its permeability to fluid flow. The intrinsic equilibrium modulus and the permeability both were highly correlated with the water content of the tissue; as water content increased, the matrix of the tissue became softer and more permeable. There was only a marginal decrease in the equilibrium modulus of the tissue with increasing age and surface degeneration. The permeability of the cartilage matrix was not significantly correlated with age or degeneration.
  CLINICAL RELEVANCE: We concluded that the visual or histological appearance of a cartilage specimen may be a poor indicator of its ability to function as the bearing material in the intact joint. A more reliable indicator of the functional properties of a specimen can be obtained either by direct mechanical testing or by biochemical analysis of its composition.


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  Variations in the intrinsic mechanical properties of human articular cartilage with age, degeneration, and water content


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  The menisci of the knee play an important role in joint function and our understanding of knee mechanics and tissue interactions can be enhanced through computational models of the tibio-menisco-femoral structure. Several finite element models of the knee that include meniscus-cartilage contact exist, but these models are typically limited to simplified boundary conditions. Movement simulation and musculoskeletal modeling can predict muscle forces, but are typically performed using the multibody method with simplified representation of joint structures. This study develops a subject specific computational model of the knee with menisci that can be incorporated into neuromusculoskeletal models within a multibody framework. Meniscus geometries from a 78-year-old female right cadaver knee were divided into 61 discrete elements (29 medial and 32 lateral) that were connected through 6x6 stiffness matrices. An optimization and design of experiments approach was used to determine parameters for the 6x6 stiffness matrices such that the force-displacement relationship of the meniscus matched that of a linearly elastic transversely isotropic finite element model for the same cadaver knee. Similarly, parameters for compliant contact models of tibio-menisco-femoral articulations were derived from finite element solutions. As a final step, a multibody knee model was developed and placed within a dynamic knee simulator model and the tibio-femoral and patello-femoral kinematics compared to an identically loaded cadaver knee. RMS errors between finite element displacement and multibody displacement after parameter optimization were 0.017 mm for the lateral meniscus and 0.051 mm for the medial meniscus. RMS errors between model predicted and experimental cadaver kinematics during a walk cycle were less than 11 mm translation and less than 7 degrees orientation. A small improvement in kinematics, compared to experimental measurements, was seen when the menisci were included versus a model without the menisci. With the menisci the predicted tibio-femoral contact force was significantly reduced on the lateral side (937 N peak force versus 633 N peak force), but no significant reduction was seen on the medial side.


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  The function of articular cartilage is to support and distribute loads and to provide lubrication in the diarthrodial joints. Cartilage function is described by proper mechanical and rheological properties, strain and depth-dependent, which are not completely assessed. Unconfined and confined compression are commonly used to evaluate the Young's modulus (E) and the aggregate modulus (H(A)), respectively. The Poisson's ratio (nu) can be calculated indirectly from the equilibrium compression data, or using the biphasic indentation technique; it has recently been optically evaluated by using video microscopy during unconfined compression. The transient response of articular cartilage during confined compression depends on its permeability k; a constant value of k can be easily identified by a simple analytical model of confined compression tests, whereas more complex models or direct measurements (permeation tests) are needed to study the permeability dependence on deformation. A poroelastic finite element model of articular cartilage was developed for this purpose. The elastic parameters (E,nu) of the model were evaluated performing unconfined compression creep tests on human articular cartilage disks, whereas k was identified from the confined test response. Our combined experimental and computational method can be used to identify the parameters that define the permeability dependence on deformation, as a function of depth from articular surface.


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  Articular cartilage is a complex composite material in engineering terms. It is inhomogeneous, anisotropic and demonstrates a time-dependent nonlinear relationship between stress and strain. This paper reviews the application of the finite-element method to the loading of articular cartilage, and highlights the potential of this numerical technique in the investigation of osteoarthritis.


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  Strain amplitude and strain rate dependent nonlinear behavior and load-induced mechanical property alterations of full-thickness bovine articular cartilage attached to bone were investigated in unconfined compression. A sequence of test compressions of finite deformation (ranging from 0.9% to 34.5% nominal strain) was performed at strain rates ranging from approximately 0.053%/s to 5.8%/s. Peak and equilibrium loads were analyzed to determine strain amplitude and strain rate dependence of linear versus nonlinear responses. The test protocol was designed to reveal changes in mechanical properties due to these finite deformations by interspersing small-amplitude witness ramps of approximately 1.1% deformation and approximately 0.44%/s strain rate between the test ramps ("witness" meaning to assess any mechanical property changes). We found that peak loads displayed high nonlinearity, stiffening with both increasing compression amplitude and more so with increasing strain rate. The response to witness ramps suggested that mechanical weakening occurred when compression amplitude reached 1.9-2.9% strain and beyond, and that weakening was much more significant at higher strain rate. These findings delineate regimes of linear versus nonlinear behavior of cartilage, and indicate the types of loads which can cause mechanical property alterations. Biological implications of this study are that strain amplitude and strain rate dependent stiffening may be essential to bear physiological loads and to protect cells and matrix from mechanical damage. Structural changes reflected by mechanical weakening at small compression could also initiate remodeling or disease processes.


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  Increasing strain and strain rate strengthen transient stiffness but weaken the response to subsequent compression for articular cartilage in unconfined compression


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  We evaluated whether the use of cartilage thickness measurement would improve the ability of the arthroscopic indentation technique to estimate the intrinsic stiffness of articular cartilage. First, cartilage thickness and ultrasound reflection from the surface of bovine humeral head were registered in situ using a high-frequency ultrasound probe. Subsequently, cartilage was indented in situ at the sites of the ultrasound measurements using arthroscopic instruments with plane-ended and spherical-ended indenters. Finally, full-thickness cartilage disks (n=30) were extracted from the indented sites (thickness=799-1654microm) and the equilibrium Young's modulus was determined with a material testing device in unconfined compression geometry. We applied analytical and numerical indentation models for the theoretical correction of experimental indentation measurements. An aspect-ratio (the ratio of indenter radius to cartilage thickness) correction improved the correlation of the indenter force with the equilibrium Young's modulus from r(2)=0.488 to r(2)=0.642-0.648 (n=30) for the plane-ended indenter (diameter=1.000mm, height=0.300mm) and from r(2)=0.654 to r(2)=0.684-0.692 (n=30) for the spherical-ended indenter (diameter=0.500mm, height=0.100mm), depending on the indentation model used for the correction. The linear correlation between the ultrasound reflection and the Young's modulus was r(2)=0.400 (n=30). These results suggest that with large indenters, knowledge of the cartilage thickness improves the reliability of the indentation measurements, especially in pathological situations where cartilage thickness may be significantly lower than normal. Ultrasound measurements also provide diagnostically important information about cartilage thickness as well as knowledge of the integrity of the superficial zone of cartilage.


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  Estimation of the Young's modulus of articular cartilage using an arthroscopic indentation instrument and ultrasonic measurement of tissue thickness


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  Articular cartilage functions as a load-bearing tissue by virtue of a functional coupling between its hydrated proteoglycan component and its zonally differentiated fibrillar network. How degeneration influences this relationship at the macro-, micro-, and ultrastructural levels is investigated in this study. Healthy bovine patellae (N=9) and patellae exhibiting varying degrees of degeneration (N=16) formed the basis of the study. Cartilage-on-bone blocks obtained from each patella were subjected to creep loading under a nominal stress of 4.5 MPa via a rectangular planar indenter which incorporated a narrow channel relief space to create a defined region where the cartilage would not be directly loaded. Following the attainment of creep equilibrium each sample was chemically fixed while under load so as to preserve the deformed state of the cartilage matrix. The structural response of the matrix was then analysed using differential interference contrast (DIC) optical microscopy and scanning electron microscopy (SEM). The morphology of the cartilage matrix extruded into the channel relief region was dramatically influenced by the severity of degeneration. The microscopic and ultrastructural characteristics of the extruded matrix showed that the load response of bulk cartilage is determined primarily by the microstructural integrity of the strain-limiting tangential layer and the nano-level interconnectivity of the fibrillar network. In conclusion, this study showed that three mechanically significant structural features of cartilage are important: (1) the strain limiting surface layer; (2) the micro-level boundaries in its zonally differentiated structure, and (3) the extent of fibrillar interconnectivity. Degeneration degrades or destroys the articular surface and ‘destructures’ the fibrillar network such that the latter functions less effectively as a proteoglycan entrapment system.


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  Macro-, micro- and ultrastructural investigation of how degeneration influences the response of cartilage to loading


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  Excessive chronic loading is thought to be one factor responsible for the onset of osteoarthritis. For example, studies using treadmill running have shown an increased risk for osteoarthritis, thereby suggesting that muscle-induced joint loading may play a role in osteoarthritis onset and progression. However, in these studies, muscle-induced loading was not carefully quantified. Here, we present a model of controlled muscular loading which allows for the accurate quantification of joint loading. The aim of this study was to evaluate the effects of long-term, cyclic, isometric and dynamic, muscle-induced joint loading of physiologic magnitude but excessive intensity on cartilage integrity and cell viability in the rabbit knee. 24 rabbits were divided into an (i) eccentric, (ii) concentric, or (iii) isometric knee extensor contraction group (50 min of cyclic, submaximal stimulation 3 times/week for four weeks=19,500 cycles) controlled by the stimulation of a femoral nerve cuff electrode on the right hind limb. The contralateral knee was used as a non-loaded control. The knee articular cartilages were analysed by confocal microscopy for chondrocyte death, and histologically for Mankin Score, cartilage thickness and cell density. All loaded knees had significantly increased cell death rates and Mankin Scores compared to the non-loaded joints. Cartilage thicknesses did not systematically differ between loaded and control joints. Chondrocyte death and Mankin Scores were significantly increased in the loaded joints, thereby linking muscular exercise of physiologic magnitude but excessive intensity to cartilage degeneration and cell death in the rabbit knee.


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  Long-term repetitive mechanical loading of the knee joint by in vivo muscle stimulation accelerates cartilage degeneration and increases chondrocyte death in a rabbit model


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  To examine the relative susceptibility of cartilage and meniscus tissues to mechanical injury by applying a single, controlled overload and observing cellular, biochemical, and mechanical changes. Cartilage and meniscus tissue explants in radial confinement were subjected to a range of injury by indenting to 40% strain at three different strain rates: 0.5%/s (slow), 5%/s (medium), or 50%/s (fast). Following injury, samples were cultured for either 1 or 9days. Explants were assayed for cell metabolic activity, water content, and sulfated glycosaminoglycan (sGAG) content. Mechanical properties of explants were determined in torsional shear and unconfined compression. Conditioned medium was assayed for sGAG and lactate dehydrogenase (LDH) release. Peak injury force increased with strain rate but both tissues displayed little to no macroscopic damage. Cell metabolism was lowest in medium and fast groups on day 1. Cell lysis increased with peak injury force and loading rate in both tissues. In contrast, sGAG content and release did not significantly vary with loading rate. Additionally, mechanical properties did not significantly vary with loading rate in either tissue. By use of a custom confinement chamber, large peak forces were obtained without macroscopic destruction of the explants. At the loads achieved in this studied, cell damage was induced without detectable physical or compositional changes. These results indicate that sub-failure injury can induce biologic damage that may not be readily detected and could be an early event in osteoarthritis genesis.


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  http://ac.els-cdn.com/S1063458412000258/1-s2.0-S1063458412000258-main.pdf?_tid=d2f56404-903c-11e7-bf1d-00000aacb362&acdnat=1504397837_c1a7ada7c95fe2e2ed9fa4b413503e46


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  A common effect of arthritic disease processes in synovial joints is deterioration of the articular cartilage. Therefore, an improved understanding of the relationships between the composition and structure of articular cartilage and the mechanical behaviour is a subject of considerable interest. The numerical modelling tool of finite element (FE) analysis has been widely applied to analyse the behaviour of articular cartilage under compressive stress. FE analysis enables parameters and boundary conditions to be investigated which are not accessible experimentally or analytically. The biphasic theory describes the constitutive behaviour of soft hydrated biological tissues, such as articular cartilage, and has been successfully implemented using FE analysis. The development of successively more comprehensive biphasic models is described here detailing the use of FE analysis in modelling experimental configurations such as indentation. Key work in the area is reviewed in this paper.


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  Macroscopic structural damage to the cartilage articular surface can occur due to slicing in surgery, cracking in mechanical trauma, or fibrillation in early stage osteoarthrosis. These alterations may render cartilage matrix and chondrocytes susceptible to subsequent mechanical injury and contribute to progression of degenerative disease. To examine this hypothesis, single 300 microm deep vertical slices were introduced across a diameter of the articular surface of osteochondral explant disks on day 6 after dissection. Then a single uniaxial unconfined ramp compression at 7 x 10(-5) or 7 x 10(-2) s(-1) strain rate to a peak stress of 3.5 or 14 MPa was applied on day 13 during which mechanical behavior was monitored. Effects of slices alone and together with compression were measured in terms of explant swelling and cell viability on days 10 and 17. Slicing alone induced tissue swelling without significant cell death, while compression alone induced cell death without significant tissue swelling. Under low strain rate loading, no differences in the response to injurious compression were found between sliced and unsliced explants. Under high strain rate loading, slicing rendered cartilage more easily compressible and appeared to slightly reduce compression-induced cell and matrix injury. Findings highlight microphysical factors important to cartilage mechanical injury, and suggest ways that macroscopic structural damage may accelerate or, in certain cases, possibly slow the progression of cartilage degeneration.


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  Effects of damage in the articular surface on the cartilage response to injurious compression in vitro


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  Though changes in normal joint motions and loads (e.g., following anterior cruciate ligament injury) contribute to the development of knee osteoarthritis, the precise mechanism by which these changes induce osteoarthritis remains unknown. As a first step toward identifying this mechanism, this study evaluates computational wear simulations of a patellofemoral joint specimen wear tested on a knee simulator machine. A multibody dynamic model of the specimen mounted in the simulator machine was constructed in commercial computer-aided engineering software. A custom elastic foundation contact model was used to calculate contact pressures and wear on the femoral and patellar articular surfaces using geometry created from laser scan and MR data. Two different wear simulation approaches were investigated--one that wore the surface geometries gradually over a sequence of 10 one-cycle dynamic simulations (termed the "progressive" approach), and one that wore the surface geometries abruptly using results from a single one-cycle dynamic simulation (termed the "non-progressive" approach). The progressive approach with laser scan geometry reproduced the experimentally measured wear depths and areas for both the femur and patella. The less costly non-progressive approach predicted deeper wear depths, especially on the patella, but had little influence on predicted wear areas. Use of MR data for creating the articular and subchondral bone geometry altered wear depth and area predictions by at most 13%. These results suggest that MR-derived geometry may be sufficient for simulating articular cartilage wear in vivo and that a progressive simulation approach may be needed for the patella and tibia since both remain in continuous contact with the femur.


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  Magnetic resonance imaging (MRI) is one of the most potential methods for non-invasive diagnosis of cartilage disorders. Several methods have been established for clinical use; T1 relaxation time imaging with negatively charged contrast agent (delayed gadolinium enhanced MRI of cartilage, dGEMRIC) has been shown to be sensitive to proteoglycan (PG) content while T2 relaxation time has been demonstrated to express properties of the collagen fibril network. The use of native T1 relaxation time has received less attention. In the present study, magnetic resonance (MR) parameters of different types of patellar cartilage were studied with respect to the mechanical properties of the tissue. The general usefulness of the parameters to predict mechanical properties was investigated using cartilage from different species and stages of maturation. dGEMRIC, T2 and native T1 relaxation times of healthy mature human, juvenile porcine and juvenile bovine articular cartilage samples were measured at 9.4T at 25°C. Mechanical properties (Young's modulus and dynamic modulus) of the samples were measured in unconfined compression using a material testing device. The relationships between MRI and mechanical parameters and potential differences between different types of tissues were tested statistically. Significant, but varying relationships were established between T1 or T2 relaxation time and mechanical properties, depending on tissue type. The values of mechanical parameters were in line with the results previously reported in the literature. Unexpectedly, dGEMRIC showed no statistically significant association with the mechanical properties. Variation in the assumption of native T1 value did not induce significant differences in the calculated contrast agent concentration, and consequently did not affect prediction of mechanical properties. For patellae, a complex variation in the relationships between T2 and mechanical properties in different groups was revealed. The results support the conclusion that juvenile animal tissue, exhibiting a highly complex collagenous architecture, may not always serve as a realistic model for mature human tissue with a typical three-zone network organization, and other than bulk metrics are required for the analysis of cartilage T2. As the multilayered collagen network can strongly control the mechanical characteristics of juvenile tissue, it may mask the mechanical role of PGs and explain why dGEMRIC could not predict mechanical parameters in patellar cartilage.


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  Estimation of mechanical properties of articular cartilage with MRI – dGEMRIC, T2 and T1 imaging in different species with variable stages of maturation


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  http://ac.els-cdn.com/S1063458407001227/1-s2.0-S1063458407001227-main.pdf?_tid=079712ba-903e-11e7-9479-00000aab0f27&acdnat=1504398354_fb0e7abe5b21ca954eafed61c82c4295


value:
  Mechanical behavior of articular cartilage was characterized in unconfined compression to delineate regimes of linear and nonlinear behavior, to investigate the ability of a fibril-reinforced biphasic model to describe measurements, and to test the prediction of biphasic and poroelastic models that tissue dimensions alter tissue stiffness through a specific scaling law for time and frequency. Disks of full-thickness adult articular cartilage from bovine humeral heads were subjected to successive applications of small-amplitude ramp compressions cumulating to a 10 percent compression offset where a series of sinusoidal and ramp compression and ramp release displacements were superposed. We found all equilibrium behavior (up to 10 percent axial compression offset) to be linear, while most nonequilibrium behavior was nonlinear, with the exception of small-amplitude ramp compressions applied from the same compression offset. Observed nonlinear behavior included compression-offset-dependent stiffening of the transient response to ramp compression, nonlinear maintenance of compressive stress during release from a prescribed offset, and a nonlinear reduction in dynamic stiffness with increasing amplitudes of sinusoidal compression. The fibril-reinforced biphasic model was able to describe stress relaxation response to ramp compression, including the high ratio of peak to equilibrium load. However, compression offset-dependent stiffening appeared to suggest strain-dependent parameters involving strain-dependent fibril network stiffness and strain-dependent hydraulic permeability. Finally, testing of disks of different diameters and rescaling of the frequency according to the rule prescribed by current biphasic and poroelastic models (rescaling with respect to the sample's radius squared) reasonably confirmed the validity of that scaling rule. The overall results of this study support several aspects of current theoretical models of articular cartilage mechanical behavior, motivate further experimental characterization, and suggest the inclusion of specific nonlinear behaviors to models.


value:
  Unconfined compression of articular cartilage: nonlinear behavior and comparison with a fibril-reinforced biphasic model


value:
  Understanding of tibiofemoral joint mechanics at multiple spatial scales is essential for developing effective preventive measures and treatments for both pathology and injury management. Currently, there is a distinct lack of specimen-specific biomechanical data at multiple spatial scales, e.g., joint, tissue, and cell scales. Comprehensive multiscale data may improve the understanding of the relationship between biomechanical and anatomical markers across various scales. Furthermore, specimen-specific multiscale data for the tibiofemoral joint may assist development and validation of specimen-specific computational models that may be useful for more thorough analyses of the biomechanical behavior of the joint. This study describes an aggregation of procedures for acquisition of multiscale anatomical and biomechanical data for the tibiofemoral joint. Magnetic resonance imaging was used to acquire anatomical morphology at the joint scale. A robotic testing system was used to quantify joint level biomechanical response under various loading scenarios. Tissue level material properties were obtained from the same specimen for the femoral and tibial articular cartilage, medial and lateral menisci, anterior and posterior cruciate ligaments, and medial and lateral collateral ligaments. Histology data were also obtained for all tissue types to measure specimen-specific cell scale information, e.g., cellular distribution. This study is the first of its kind to establish a comprehensive multiscale data set for a musculoskeletal joint and the presented data collection approach can be used as a general template to guide acquisition of specimen-specific comprehensive multiscale data for musculoskeletal joints.


value:
  A Comprehensive Specimen-Specific Multiscale Data Set for Anatomical and Mechanical Characterization of the Tibiofemoral Joint


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