Cartilage Stiffness Research Articles

Engineered cartilage utilizing fetal cartilage-derived progenitor cells for cartilage repair

The aim of this study was to develop a fetal cartilage-derived progenitor cell (FCPC) based cartilage gel through self-assembly for cartilage repair surgery, with clinically useful properties including adhesiveness, plasticity, and continued chondrogenic remodeling after transplantation. Characterization of the gels according to in vitro self-assembly period resulted in increased chondrogenic features over time. Adhesion strength of the cartilage gels were significantly higher compared to alginate gel, with the 2-wk group showing a near 20-fold higher strength (1.8 ± 0.15 kPa vs. 0.09 ± 0.01 kPa, p < 0.001). The in vivo remodeling process analysis of the 2 wk cultured gels showed increased cartilage repair characteristics and stiffness over time, with higher integration-failure stress compared to osteochondral autograft controls at 4 weeks (p < 0.01). In the nonhuman primate investigation, cartilage repair scores were significantly better in the gel group compared to defects alone after 24 weeks (p < 0.001). Cell distribution analysis at 24 weeks showed that human cells remained within the transplanted defects only. A self-assembled, FCPC-based cartilage gel showed chondrogenic repair potential as well as adhesive properties, beneficial for cartilage repair.

Targeting downstream subcellular YAP activity as a function of matrix stiffness with Verteporfin-encapsulated chitosan microsphere attenuates osteoarthritis

Changes in the stiffness of chondrocyte extracellular matrix (ECM) are involved in the pathological progression of osteoarthritis (OA). However, the downstream responses of cartilage ECM stiffness are still unclear. YAP (Yes-associated protein) has been extensively studied as a mechanotransducer, we thus hypothesized that by targeting the downstream molecule activity of ECM stiffness could maintain chondrocyte phenotype and prevent cartilage degeneration in OA. Here, we showed that human cartilage matrix stiffened during pathological progression of OA, and the chondrocyte YAP activity was associated with ECM stiffness. We then mimicked the physiological and pathological stiffness of human cartilage by using PDMS-based substrates, and found that YAP was activated in chondrocytes seeded on stiff substrate, gradually losing their phenotype. In addition, it was observed that YAP was also significantly activated in mice OA development, and conditional knockout (cKO) of YAP in mice preserved collagen II expression and protected cartilage from degeneration in the OA model. Furthermore, intra-articular injection of YAP-selective inhibitor, Verteporfin, significantly maintained cartilage homeostasis in mice OA model. This study indicates that the application of mechanotransducer-targeted drugs could be a potential therapeutic approach for cartilage repair in OA.

FINITE ELEMENT ANALYSIS OF FULL-LAYER REPAIR BASED ON IMPROVED ARTICULAR CARTILAGE MODEL

In this paper, the tangential zone of cartilage is introduced into the fiber-reinforced model of articular cartilage. Considering the distribution content of the main fiber and the secondary fiber in the tangential layer of cartilage, the permeability and fiber stiffness of the layer are set in parallel and perpendicular directions, respectively, to more accurately reflect the mechanical behavior of cartilage. The parameters are set to reflect the mechanical behavior of the cartilage more realistically. We use a modified articular cartilage model to simulate the mechanical properties of implanted cartilage with different elastic modulus. The simulation results show that the selection of implants with different elastic modulus will affect the repair of cartilage. Appropriately increasing the elastic modulus of implanted cartilage, can increase the bearing capacity of the repaired area and reduce the stress concentration at the junction. The elastic modulus of the implant should be moderate, not too large or too small, and the damage of stress concentration on the repair surface should be considered. Through simulation, the mechanical state of the repaired cartilage under pressure can be obtained comprehensively, which provides a theoretical basis for clinical pathology.

Anterior cruciate ligament transection of rabbits alters composition, structure and biomechanics of articular cartilage and chondrocyte deformation 2 weeks post-surgery in a site-specific manner

Anterior cruciate ligament (ACL) injury often leads to post-traumatic osteoarthritis (OA) and articular cartilage degradation, changing biomechanics of the tissue and chondrocytes, and altering the fixed charged density (FCD) and collagen network. However, changes in these properties are not known at a very early time point after ACL rupture, but recognizing early changes might be crucial for successful intervention. We investigated the effects of ACL transection (ACLT) in rabbits on the site-specific biomechanical properties of articular cartilage and chondrocytes, FCD content and collagen network organization, two weeks post-surgery.Unilateral ACLT was performed in eight rabbits, and femoral condyles, tibial plateaus, femoral grooves and patellae were harvested from experimental and contralateral knee joints. An intact control group was used as a reference. We analyzed chondrocyte morphology under pre- and static loading, cartilage biomechanical properties, FCD content and collagen fibril orientation.ACLT caused FCD loss in the lateral and medial femoral condyle, lateral tibial plateau, femoral groove and patellar cartilage (p < 0.05). Minor changes in the collagen orientation occurred in the femoral groove and lateral and medial femoral condyle cartilage (p < 0.05). Cartilage stiffness was reduced in the lateral and medial femoral condyles, and chondrocyte biomechanics was altered in the lateral femoral condyle and patellar cartilage (p < 0.05).We observed loss of FCD from articular cartilage two weeks after ACLT at several joint locations. These changes may have led to decreased cartilage stiffness and altered cell deformation behavior, especially in the femoral condyles.

The Effect of Articular Cartilage Focal Defect Size and Location in Whole Knee Biomechanics Models.

Articular cartilage focal defects are common soft tissue injuries potentially linked to osteoarthritis (OA) development. Although several defect characteristics likely contribute to osteoarthritis, their relationship to local tissue deformation remains unclear. Using finite element models with various femoral cartilage geometries, we explore how defects change cartilage deformation and joint kinematics assuming loading representative of the maximum joint compression during the stance phase of gait. We show how defects, in combination with location-dependent cartilage mechanics, alter deformation in affected and opposing cartilages, as well as joint kinematics. Small and average sized defects increased maximum compressive strains by approximately 50% and 100%, respectively, compared to healthy cartilage. Shifts in the spatial locations of maximum compressive strains of defect containing models were also observed, resulting in loading of cartilage regions with reduced initial stiffnesses supporting the new, elevated loading environments. Simulated osteoarthritis (modeled as a global reduction in mean cartilage stiffness) did not significantly alter joint kinematics, but exacerbated tissue deformation. Femoral defects were also found to affect healthy tibial cartilage deformations. Lateral femoral defects increased tibial cartilage maximum compressive strains by 25%, while small and average sized medial defects exhibited decreases of 6% and 15%, respectively, compared to healthy cartilage. Femoral defects also affected the spatial distributions of deformation across the articular surfaces. These deviations are especially meaningful in the context of cartilage with location-dependent mechanics, leading to increases in peak contact stresses supported by the cartilage of between 11% and 34% over healthy cartilage.

3D grating-based X-ray phase-contrast computed tomography for high-resolution quantitative assessment of cartilage: An experimental feasibility study with 3T MRI, 7T MRI and biomechanical correlation.

ObjectiveAim of this study was, to demonstrate the feasibility of high-resolution grating-based X-ray phase-contrast computed tomography (PCCT) for quantitative assessment of cartilage.Materials and methodsIn an experimental setup, 12 osteochondral samples were harvested from n = 6 bovine knees (n = 2 each). From each knee, one cartilage sample was degraded using 2.5% Trypsin. In addition to PCCT and biomechanical cartilage stiffness measurements, 3T and 7T MRI was performed including MSME SE T2 and ME GE T2* mapping sequences for relaxationtime measurements. Paired t-tests and receiver operating characteristics (ROC) curves were used for statistical analyses.ResultsPCCT provided high-resolution images for improved morphological cartilage evaluation as compared to 3T and 7T MRI. Quantitative analyses revealed significant differences between the superficial and the deep cartilage layer for T2 mapping as well as for PCCT (P<0.05). No significant difference was detected for PCCT between healthy and degraded samples (P>0.05). MRI and stiffness measurements showed significant differences between healthy and degraded osteochondral samples. Accuracy in the prediction of cartilage degradation was excellent for MRI and biomechanical analyses.ConclusionIn conclusion, high-resolution grating-based X-ray PCCT cartilage imaging is feasible. In addition to MRI and biomechanical analyses it provides complementary, water content independent, information for improved morphological and quantitative characterization of articular cartilage ultrastructure.

Cartilage Stiffness Effect on Foot Biomechanics of Chinese Bound Foot: A Finite Element Analysis.

The purpose of this study is to investigate the effect of cartilage stiffness on inner foot biomechanics of Chinese bound foot while balanced standing using finite element method. A three-dimensional FE model of bound foot involving 28 bones, 72 ligaments, 5 plantar fascia, cartilages, and encapsulated soft tissue was constructed and validated. To conduct the sensitivity analysis of cartilage stiffness, the incremental Young’s modulus of 1, 5, 10, and 15 MPa were assigned to the cartilage. 25% of the body weight was applied to the Achilles tendon to adjust the anterior- posterior displacement of center of pressure agreeable with the measured result. As the Young’s modulus of cartilage increased, the peak von Mises stress in the fifth metatarsal increased obviously, while that in the calcaneus remains unchanged. The plantar fascia experienced reduced total tension with stiffer cartilage. The cartilage stiffening also caused a general increase of contact pressure at mid- and forefoot joints. Cartilage stiffening due to foot binding gave rise to risks of foot pain and longitude arch damage. Knowledge of this study contributes to the understanding of bound foot biomechanical behavior and demonstrating the mechanism of long-term injury and function damage in terms of weight-bearing due to foot binding.

Aging does not change the compressive stiffness of mandibular condylar cartilage in horses

Aging can cause an increase in the stiffness of hyaline cartilage as a consequence of increased protein crosslinks. By induction of crosslinking, a reduction in the diffusion of solutions into the hyaline cartilage has been observed. However, there is a lack of knowledge about the effects of aging on the biophysical and biochemical properties of the temporomandibular joint (TMJ) cartilage. Hence, the aim of this study was to examine the biophysical properties (thickness, stiffness, and diffusion) of the TMJ condylar cartilage of horses of different ages and their correlation with biochemical parameters. We measured the compressive stiffness of the condyles, after which the diffusion of two contrast agents into cartilage was measured using Contrast Enhanced Computed Tomography technique. Furthermore, the content of water, collagen, GAG, and pentosidine was analyzed. Contrary to our expectations, the stiffness of the cartilage did not change with age (modulus remained around 0.7MPa). The diffusion of the negatively charged contrast agent (Hexabrix) also did not alter. However, the diffusion of the uncharged contrast agent (Visipaque) decreased with aging. The flux was negatively correlated with the amount of collagen and crosslink level which increased with aging. Pentosidine, collagen, and GAG were positively correlated with age whereas thickness and water content showed negative correlations. Our data demonstrated that aging was not necessarily reflected in the biophysical properties of TMJ condylar cartilage. The combination of the changes happening due to aging resulted in different diffusive properties, depending on the nature of the solution.

The impact of surgical manipulation on lower lateral cartilage stiffness

Cephalic trimming of the alar (or lower lateral) cartilage may cause weakening leading to external nasal valve collapse. Numerous methods have been proposed to combat this weakening in order to maintain lateral crural stiffness. The purpose of this study was to quantify the effect of mucosal stripping, cephalic trimming, cephalic turn-in flap, and lateral crural strut grafting on lateral crural stiffness. In situ cyclic compressive loading was performed on eight lateral crura in 4 fresh frozen cadaveric specimens. Testing was performed on the unaltered degloved cartilage (intact) and following each of the following interventions: mucosal stripping, cephalic turn-in flap, cephalic trimming, and lateral crural strut grafting. Linear regression of the generated force-displacement curves was used to calculate stiffness. Each intervention was compared to the intact cartilage. Alar cartilage of all of the specimens demonstrated a linear response to compressive loading. Intact cartilage had a mean stiffness of 3.53 N/mm. Mucosal stripping and cephalic turn-in flaps yielded similar stiffness values to intact cartilage. Cephalic trimming reduced stiffness in all cases by a mean of 1.09 N/mm (p = 0.003). Lateral crural strut grafting significantly increased stiffness by a mean of 3.67 N/mm (p = 0.0001). Cephalic trimming leads to decreased lateral crural stiffness in cadaveric specimens. Cephalic turn-in flaps restore pre-trimmed stiffness, and lateral crural strut grafting increases overall stiffness of the cartilage. These findings should be considered in patients undergoing rhinoplasty, particularly if there are concerns regarding potential external valve collapse.

Non-enzymatic cross-linking of collagen type II fibrils is tuned via osmolality switch.

ABSTRACTAn important aspect in cartilage ageing is accumulation of advanced glycation end products (AGEs) after exposure to sugars. Advanced glycation results in cross‐links formation between the collagen fibrils in articular cartilage, hampering their flexibility and making cartilage more brittle. In the current study, we investigate whether collagen cross‐linking after exposure to sugars depends on the stretching condition of the collagen fibrils. Healthy equine cartilage specimens were exposed to l‐threose sugar and placed in hypo‐, iso‐, or hyper‐osmolal conditions that expanded or shrank the tissue and changed the 3D conformation of collagen fibrils. We applied micro‐indentation tests, contrast enhanced micro‐computed tomography, biochemical measurement of pentosidine cross‐links, and cartilage surface color analysis to assess the effects of advanced glycation cross‐linking under these different conditions. Swelling of extracellular matrix due to hypo‐osmolality made cartilage less susceptible to advanced glycation, namely, the increase in effective Young's modulus was approximately 80% lower in hypo‐osmolality compared to hyper‐osmolality and pentosidine content per collagen was 47% lower. These results indicate that healthy levels of glycosaminoglycans not only keep cartilage stiffness at appropriate levels by swelling and pre‐stressed collagen fibrils, but also protect collagen fibrils from adverse effects of advanced glycation. These findings highlight the fact that collagen fibrils and therefore cartilage can be protected from further advanced glycation (“ageing”) by maintaining the joint environment at sufficiently low osmolality. Understanding of mechanochemistry of collagen fibrils provided here might evoke potential ageing prohibiting strategies against cartilage deterioration. © 2018 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 36:1929–1936, 2018.

Mechanical stiffness of TMJ condylar cartilage increases after artificial aging by ribose

ObjectiveAging is accompanied by a series of changes in mature tissues that influence their properties and functions. Collagen, as one of the main extracellular components of cartilage, becomes highly crosslinked during aging. In this study, the aim was to examine whether a correlation exists between collagen crosslinking induced by artificial aging and mechanical properties of the temporomandibular joint (TMJ) condyle. To evaluate this hypothesis, collagen crosslinks were induced using ribose incubation. MethodsPorcine TMJ condyles were incubated for 7 days with different concentrations of ribose. The compressive modulus and stiffness ratio (incubated versus control) was determined after loading. Glycosaminoglycan and collagen content, and the number of crosslinks were analyzed. Tissue structure was visualized by microscopy using different staining methods. ResultsConcomitant with an increasing concentration of ribose, an increase of collagen crosslinks was found. The number of crosslinks increased almost 50 fold after incubation with the highest concentration of ribose. Simultaneously, the stiffness ratio of the samples showed a significant increase after incubation with the ribose. Pearson correlation analyses showed a significant positive correlation between the overall stiffness ratio and the crosslink level; the higher the number of crosslinks the higher the stiffness. ConclusionThe present model, in which ribose was used to mimic certain aspects of age-related changes, can be employed as an in vitro model to study age-related mechanical changes in the TMJ condyle.

Sustained intra-cartilage delivery of low dose dexamethasone using a cationic carrier for treatment of post traumatic osteoarthritis.

Disease-modifying osteoarthritis drugs (DMOADs) should reach their intra-tissue target sites at optimal doses for clinical efficacy. The dense, negatively charged matrix of cartilage poses a major hindrance to the transport of potential therapeutics. In this work, electrostatic interactions were utilised to overcome this challenge and enable higher uptake, full-thickness penetration and enhanced retention of dexamethasone (Dex) inside rabbit cartilage. This was accomplished by using the positively charged glycoprotein avidin as nanocarrier, conjugated to Dex by releasable linkers. Therapeutic effects of a single intra-articular injection of low dose avidin-Dex (0.5mg Dex) were evaluated in rabbits 3 weeks after anterior cruciate ligament transection (ACLT). Immunostaining confirmed that avidin penetrated the full cartilage thickness and was retained for at least 3 weeks. Avidin-Dex suppressed injury-induced joint swelling and catabolic gene expression to a greater extent than free Dex. It also significantly improved the histological score of cell infiltration and morphogenesis within the periarticular synovium. Micro-computed tomography confirmed the reduced incidence and volume of osteophytes following avidin-Dex treatment. However, neither treatment restored the loss of cartilage stiffness following ACLT, suggesting the need for a combinational therapy with a pro-anabolic factor for enhancing matrix biosynthesis. The avidin dose used caused significant glycosaminoglycan (GAG) loss, suggesting the use of higher Dex : avidin ratios in future formulations, such that the delivered avidin dose could be much less than that shown to affect GAGs. This charge-based delivery system converted cartilage into a drug depot that could also be employed for delivery to nearby synovium, menisci and ligaments, enabling clinical translation of a variety of DMOADs.

Hydrogen Peroxide Induced Oxidative Damage on Mechanical Properties of the Articular Cartilage

Articular cartilage has unique mechanical and physicochemical properties which are responsible for its load carrying capabilities. This work investigates the effects of hydrogen peroxide induced oxidative damage on mechanical properties of articular cartilage. Bovine articular cartilage was exposed to hydrogen peroxide for a week. Dynamic and static mechanical tests applied to calculate articular cartilage compressive modulus. We observed higher control curve slopes than that of hydrogen peroxide curves which account for lesser stiffness values in the exposed articular cartilage. For the instantaneous experiments, results were statistically significant (p = 0.01, p > 0.05). Here report that hydrogen peroxide induced oxidative damage causes reduction in the stiffness of the articular cartilage.

Effects of non-enzymatic glycation on the micro- and nano-mechanics of articular cartilage.

The mechanical properties of articular cartilage depend on the quality of its matrix, which consists of collagens and glycosaminoglycans (GAGs). The accumulation of advanced glycation end products (AGEs) can greatly affect the mechanics of cartilage. In the current study, we simulated the accumulation of AGEs by using L-threose to cross-link collagen molecules in the cartilage matrix (in vitro). The resulting changes in the mechanical properties (stiffness) of cartilage are then measured both at the micrometer-scale (using micro-indenter) and nanometer-scale (using indentation-type atomic force microscopy). Non-enzymatic cross-linking within the cartilage matrix was confirmed by the browning of L-threose-treated samples. We observed > 3 times increase in the micro-scale stiffness and up to 12-fold increase in the nano-scale stiffness of the glycated cartilage in the peak pertaining to the collagen fibers, which is caused by cartilage network embrittlement. At the molecular level, we found that besides the collagen component, the glycation process also influenced the GAG macromolecules. Comparing cartilage samples before and after L-threose treatment revealed that artificially induced-AGEs also decelerate in vitro degradation (likely via matrix metalloproteinases), observed at both micro- and nano-scales. The combined observations suggest that non-enzymatic glycation may play multiple roles in mechanochemical functioning of articular cartilage.

Cartilage Stiffness and Knee Loads Distribution: A Discrete Model for Landing Impacts

Musculoskeletal simulations can be used to determine loads experienced by the ligaments and cartilage during athletic motions such as impact from a drop landing, hence investigating mechanisms for injury. An open-source discrete element knee model was used to perform a forward dynamic simulation of the impact phase of a drop landing. The analysis was performed for varying moduli: nominal stiffness based on the literature, stiffness increased by 10%, and decreased by 10%. As the cartilage stiffness increased, the medial compartment contact load decreased. Conversely, the lateral compartment load and medial collateral ligament (MCL) force increased, causing a shift in the load distribution. However, these changes were insignificant compared to the overall magnitude of the contact forces (&lt;4% change). The anterior cruciate ligament (ACL), posterior cruciate ligament (PCL), and lateral collateral ligament (LCL) loads remain unchanged between varying cartilage stiffness values. The medial compartment bears a majority of the load (860 N in the medial compartment versus 540 N in the lateral) during the impact phase of a drop landing, which agrees with physiological data that the medial side of the knee is more affected by osteoarthritis (OA) than the lateral side. The model was then simplified using a linear Kelvin–Voight model for the cartilage and linear pretensioned springs representing the cumulative ligament bundles. This allowed for a validation of the system and the extrapolation of the results as the mass and cartilage stiffness varied. This is one of the few studies to quantify this load distribution and shows that the results are invariant to changes in cartilage stiffness. This effect is due to the precompression system created by the coordinated action of cartilage and ligaments.

Dietary variation and mechanical properties of articular cartilage in the temporomandibular joint: implications for the role of plasticity in mechanobiology and pathobiology

Due to their nature as tissue composites, skeletal joints pose an additional challenge in terms of evaluating the functional significance of morphological variation in their bony and cartilaginous components in response to altered loading conditions. Arguably, this complexity requires more direct means of investigating joint plasticity and performance than typically employed to analyze macro- and micro-anatomical phenomena. To address a significant gap in our understanding of the plasticity of the mammalian temporomandibular joint (TMJ), we investigated the histology and mechanical properties of condylar articular cartilage in rabbits subjected to long-term variation in diet-induced masticatory stresses, specifically cyclical loading. Three cohorts of male weanlings were raised for six months on different diets until adulthood. Following euthanasia, the TMJ condyles on one side were dissected away, fixed, decalcified, dehydrated, embedded and sectioned. Safranin O staining was employed to identify variation in proteoglycan content, which in turn was used to predict patterns of articular cartilage stiffness in contralateral condylar specimens for each treatment group. Hematoxylin and eosin staining was used to quantify diet-induced changes in chondrocyte hypertrophy and cellularity. Mechanical tests document significant decreases in articular cartilage stiffness corresponding to patterns of extracellular matrix relative protein abundance in rabbits subjected to greater cyclical loading. This indicates that TMJs routinely subjected to higher masticatory stresses due to a challenging diet eventually develop postnatal decreases in the ability to counter compressive loads during postcanine biting and chewing. These findings provide novel information regarding TMJ performance, with broader implications about the costs and benefits of phenotypic plasticity as well as implications for how such biological processes affect connective tissue mechanobiology and pathobiology.

Optimal Regression Method for Near-Infrared Spectroscopic Evaluation of Articular Cartilage.

Near-infrared (NIR) spectroscopy has been successful in nondestructive assessment of biological tissue properties, such as stiffness of articular cartilage, and is proposed to be used in clinical arthroscopies. Near-infrared spectroscopic data include absorbance values from a broad wavelength region resulting in a large number of contributing factors. This broad spectrum includes information from potentially noisy variables, which may contribute to errors during regression analysis. We hypothesized that partial least squares regression (PLSR) is an optimal multivariate regression technique and requires application of variable selection methods to further improve the performance of NIR spectroscopy-based prediction of cartilage tissue properties, including instantaneous, equilibrium, and dynamic moduli and cartilage thickness. To test this hypothesis, we conducted for the first time a comparative analysis of multivariate regression techniques, which included principal component regression (PCR), PLSR, ridge regression, least absolute shrinkage and selection operator (Lasso), and least squares version of support vector machines (LS-SVM) on NIR spectral data of equine articular cartilage. Additionally, we evaluated the effect of variable selection methods, including Monte Carlo uninformative variable elimination (MC-UVE), competitive adaptive reweighted sampling (CARS), variable combination population analysis (VCPA), backward interval PLS (BiPLS), genetic algorithm (GA), and jackknife, on the performance of the optimal regression technique. The PLSR technique was found as an optimal regression tool (R2Tissue thickness = 75.6%, R2Dynamic modulus = 64.9%) for cartilage NIR data; variable selection methods simplified the prediction models enabling the use of lesser number of regression components. However, the improvements in model performance with variable selection methods were found to be statistically insignificant. Thus, the PLSR technique is recommended as the regression tool for multivariate analysis for prediction of articular cartilage properties from its NIR spectra.

Viscoelasticity of articular cartilage: Analysing the effect of induced stress and the restraint of bone in a dynamic environment.

The aim of this study was to determine the effect of the induced stress and restraint provided by the underlying bone on the frequency-dependent storage and loss stiffness (for bone restraint) or modulus (for induced stress) of articular cartilage, which characterise its viscoelasticity. Dynamic mechanical analysis has been used to determine the frequency-dependent viscoelastic properties of bovine femoral and humeral head articular cartilage. A sinusoidal load was applied to the specimens and out-of-phase displacement response was measured to determine the phase angle, the storage and loss stiffness or modulus. As induced stress increased, the storage modulus significantly increased (p < 0.05). The phase angle decreased significantly (p < 0.05) as the induced stress increased; reducing from 13.1° to 3.5°. The median storage stiffness ranged from 548 N/mm to 707 N/mm for cartilage tested on-bone and 544 N/mm to 732 N/mm for cartilage tested off-bone. On-bone articular cartilage loss stiffness was frequency independent (p > 0.05); however, off-bone, articular cartilage loss stiffness demonstrated a logarithmic frequency-dependency (p < 0.05). In conclusion, the frequency-dependent trends of storage and loss moduli of articular cartilage are dependent on the induced stress, while the restraint provided by the underlying bone removes the frequency-dependency of the loss stiffness.

Intrinsic fluorescence and mechanical testing of articular cartilage in human patients with osteoarthritis.

The degeneration of articular cartilage is the main cause of osteoarthritis (OA), a common cause of disability among elderly patients. The aim of this study is to understand the correlation between intrinsic fluorescence of articular cartilage and its biomechanical properties in patients with osteoarthritis. Cylindrical samples of articular cartilage 6 mm in diameter were extracted via biopsy punch from the femoral condyles of 6 patients with advanced OA undergoing knee replacement surgery. The mechanical stiffness and fluorescence of each cartilage plug were measured by indentation test and spectrofluorometry. Maps of fluorescence intensity, at excitation/emission wavelengths of 240-520/290-530 nm, were used to identify wavelengths of interest. The mechanical stiffness and fluorescence intensity were correlated using a Spearman analysis. The excitation/emission maps demonstrated three fluorescence peaks at excitation/emission wavelength pairs 330/390, 350/430 and 370/460 nm. The best correlation between the fluorescence intensity and stiffness of cartilage was obtained for the 330 nm excitation band [R=0.82, p=0.04]. The intrinsic fluorescence of articular cartilage may have application in optically assessing the state of cartilage in patients with osteoarthritis.

The spatio-temporal mechanical environment of healthy and injured human cartilage during sustained activity and its role in cartilage damage

Recently we presented a computational model of articular cartilage calibrated for normal human tissue explants. This model was able to capture the transient deformation of cartilage experiencing a cyclic load. The model takes into account the tension-compression nonlinearity of the cartilage and incorporates the dependency of the compressive stiffness and fluid permeability of cartilage on the deformation-dependent aggrecan concentration in cartilage tissue. As such it represents a leading constitutive model of articular cartilage. Here we build on the previous study to develop an experimentally validated computational model to simulate mechanical consolidation response of intact and previously injured cartilage under sustained static loading, to develop our understanding of the implications for rates of tissue damage. We see that the type of prior injuries compromise the cartilage function in different ways. Relatively rapid consolidation is predicted for cartilage with a complete meniscectomy and that with a full thickness defect, indicating the inability of cartilage with such injuries to sustain interstitial fluid pressurisation for long periods of time, as does uninjured cartilage. By comparing the consolidation response of articular cartilage predicted by computational model against experimental measurements of the apparent friction coefficient following static loading, we find a strong linear positive correlation exists between cartilage degree of consolidation (DoC) and friction coefficient at the joint. As the DoC of articular cartilages can be estimated in vivo via medical imaging, the DoC can be used as an index to non-invasively evaluate the apparent friction coefficient between opposing cartilage surfaces, and so estimate the likelihood of frictional surface wear and/or cartilage damage.