Composition of the pericellular matrix modulates the deformation behaviour of chondrocytes in articular cartilage under static loading

The aim was to assess the role of the composition changes in the pericellular matrix (PCM) for the chondrocyte deformation. For that, a three-dimensional finite element model with depth-dependent collagen density, fluid fraction, fixed charge density and collagen architecture, including parallel planes representing the split-lines, was created to model the extracellular matrix (ECM). The PCM was constructed similarly as the ECM, but the collagen fibrils were oriented parallel to the chondrocyte surfaces. The chondrocytes were modelled as poroelastic with swelling properties. Deformation behaviour of the cells was studied under 15% static compression. Due to the depth-dependent structure and composition of cartilage, axial cell strains were highly depth-dependent. An increase in the collagen content and fluid fraction in the PCMs increased the lateral cell strains, while an increase in the fixed charge density induced an inverse behaviour. Axial cell strains were only slightly affected by the changes in PCM composition. We conclude that the PCM composition plays a significant role in the deformation behaviour of chondrocytes, possibly modulating cartilage development, adaptation and degeneration. The development of cartilage repair materials could benefit from this information

The effect of fixed charge density and cartilage swelling on mechanics of knee joint cartilage during simulated gait

\u3cp\u3eThe effect of swelling of articular cartilage, caused by the fixed charge density (FCD) of proteoglycans, has not been demonstrated on knee joint mechanics during simulated walking before. In this study, the influence of the depth-wise variation of FCD was investigated on the internal collagen fibril strains and the mechanical response of the knee joint cartilage during gait using finite element (FE) analysis. The FCD distribution of tibial cartilage was implemented from sodium (\u3csup\u3e23\u3c/sup\u3eNa) MRI into a 3-D FE-model of the knee joint ( Healthy model ). For comparison, models with decreased FCD values were created according to the decrease in FCD associated with the progression of osteoarthritis (OA) ( Early OA and Advanced OA models). In addition, a model without FCD was created ( No FCD model). The effect of FCD was studied with five different collagen fibril network moduli of cartilage. Using the reference fibril network moduli, the decrease in FCD from Healthy model to Early OA and Advanced OA models resulted in increased axial strains (by +2 and +6%) and decreased fibril strains (by -3 and -13%) throughout the stance, respectively, calculated as mean values through cartilage depth in the tibiofemoral contact regions. Correspondingly, compared to the Healthy model , the removal of the FCD altogether in NoFCD model resulted in increased mean axial strains by +16% and decreased mean fibril strains by -24%. This effect was amplified as the fibril network moduli were decreased by 80% from the reference. Then mean axial strains increased by +6, +19 and +49% and mean fibril strains decreased by -9, -20 and -32%, respectively. Our results suggest that the FCD in articular cartilage has influence on cartilage responses in the knee during walking. Furthermore, the FCD is suggested to have larger impact on cartilage function as the collagen network degenerates e.g. in OA.\u3c/p\u3

Stress-relaxation of human patellar articular cartilage in unconfined compression: Prediction of mechanical response by tissue composition and structure.

Mechanical properties of articular cartilage are controlled by tissue composition and structure. Cartilage function is sensitively altered during tissue degeneration, in osteoarthritis (OA). However, mechanical properties of the tissue cannot be determined non-invasively. In the present study, we evaluate the feasibility to predict, without mechanical testing, the stress–relaxation response of human articular cartilage under unconfined compression. This is carried out by combining microscopic and biochemical analyses with composition-based mathematical modeling.Cartilage samples from five cadaver patellae were mechanically tested under unconfined compression. Depth-dependent collagen content and fibril orientation, as well as proteoglycan and water content were derived by combining Fourier transform infrared imaging, biochemical analyses and polarized light microscopy. Finite element models were constructed for each sample in unconfined compression geometry. First, composition-based fibril-reinforced poroviscoelastic swelling models, including composition and structure obtained from microscopical and biochemical analyses were fitted to experimental stress–relaxation responses of three samples. Subsequently, optimized values of model constants, as well as compositional and structural parameters were implemented in the models of two additional samples to validate the optimization.Theoretical stress–relaxation curves agreed with the experimental tests (R=0.95–0.99). Using the optimized values of mechanical parameters, as well as composition and structure of additional samples, we were able to predict their mechanical behavior in unconfined compression, without mechanical testing (R=0.98). Our results suggest that specific information on tissue composition and structure might enable assessment of cartilage mechanics without mechanical testing

Implementation and importance of the subject-specific distribution of fixed charge density of articular cartilage in the knee

Negative charges of glycosaminoglycan (GAG) side chains of proteoglycans (PGs) result in fixed charge density (FCD) of articular cartilage. FCD induces swelling of the tissue and hence plays an important role in load support of the tissue [1,2]. However, it is not known how depth-wise FCD distribution in the knee joint controls cartilage strains. Here, we implement a subject-specific FCD distribution of human knee joint cartilage, as obtained from sodium (23Na) MRI, into a fibrilreinforced poroviscoelastic model with swelling properties (FRPVES). We validate the model by comparing modeled cartilage deformations to experimentally measured deformations in vivo, and demonstrate the importance of the subjectspecific FCD distribution of knee joint cartilage under static loading

Spatial variation of fixed charge density in knee joint cartilage from sodium MRI – Implication on knee joint mechanics under static loading

\u3cp\u3eThe effects of fixed charge density (FCD) and cartilage swelling have not been demonstrated on cartilage mechanics on knee joint level before. In this study, we present how the spatial and local variations of FCD affects the mechanical response of the knee joint cartilage during standing (half of the body weight, 13 minutes) using finite element (FE) modeling. The FCD distribution of tibial cartilage of an asymptomatic subject was determined using sodium (\u3csup\u3e23\u3c/sup\u3eNa) MRI at 7T and implemented into a 3-D FE-model of the knee joint (Subject-specific model, FCD: 0.18±0.08 mEq/ml). Tissue deformation in the Subject-specific model was validated against experimental, in vivo loading of the joint conducted with a MR-compatible compression device. For comparison, models with homogeneous FCD distribution (homogeneous model) and FCD distribution obtained from literature (literature model) were created. Immediately after application of the load (dynamic response), the variations in FCD had minor effects on cartilage stresses and strains. After 13 minutes of standing, the spatial and local variations in FCD had most influence on axial strains. In the superficial tibial cartilage in the Subject-specific model, axial strains were increased up to +13% due to smaller FCD (mean −11%), as compared to the homogeneous model. Compared to the literature model, those were decreased up to −18% due to greater FCD (mean +7%). The findings demonstrate that the spatial and local FCD variations in cartilage modulates strains in knee joint cartilage. Thereby, the results highlight the mechanical importance of site-specific content of proteoglycans in cartilage.\u3c/p\u3