For the first time, depth-wise point-by-point statistical comparisons of structure and composition of human articular cartilage were conducted. The present results indicated that early OA is primarily characterized by the changes in collagen orientation and PG content in the superficial zone, while collagen content does not change until OA has progressed to its late stage. Our simulation results suggest that impact loads in OA joint could create a risk for tissue failure and cell death.

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During maturation, significant modulation of tissue structure, composition and mechanical properties takes place. Importantly, the present study provides insight into the mechanical, chemical and structural interactions that lead to functional properties of mature articular cartilage.

ABSTRACT:The equilibrium Young's modulus of articular cartilage is known to be primarily determined by proteoglycans (PGs). However, the relation between the Poisson's ratio and the composition and structure of articular cartilage is more unclear. In this study, we determined Young's modulus and Poisson's ratio of bovine articular cartilage in unconfined compression. Subsequently, the same samples, taken from bovine knee (femoral, patellar and tibial cartilage) and shoulder (humeral cartilage) joints, were processed for quantitative microscopic analysis of PGs, collagen content, and collagen architecture. The Young's modulus, Poisson's ratio, PG content (estimated with optical density measurements), collagen content, and birefringence showed significant topographical variation (p < 0.05) among the test sites. Experimentally the Young's modulus was strongly determined by the tissue PG content (r ¼ 0.86, p < 0.05). Poisson's ratio revealed a significant negative linear correlation (r ¼ À0.59, p < 0.05) with the collagen content, as assessed by the Fourier transform infrared imaging. Finite element analyses, conducted using a fibril reinforced biphasic model, indicated that the mechanical properties of the collagen network strongly affected the Poisson's ratio. We conclude that Poisson's ratio of articular cartilage is primarily controlled by the content and organization of the collagen network. ß

The collagen network and proteoglycan matrix of articular cartilage are thought to play an important role in controlling the stresses and strains in and around chondrocytes, in regulating the biosynthesis of the solid matrix, and consequently in maintaining the health of diarthrodial joints. Understanding the detailed effects of the mechanical environment of chondrocytes on cell behavior is therefore essential for the study of the development, adaptation, and degeneration of articular cartilage. Recent progress in macroscopic models has improved our understanding of depth-dependent properties of cartilage. However, none of the previous works considered the effect of realistic collagen orientation or depth-dependent negative charges in microscopic models of chondrocyte mechanics. The aim of this study was to investigate the effects of the collagen network and fixed charge densities of cartilage on the mechanical environment of the chondrocytes in a depth-dependent manner. We developed an anisotropic, inhomogeneous, microstructural fibril-reinforced finite element model of articular cartilage for application in unconfined compression. The model consisted of the extracellular matrix and chondrocytes located in the superficial, middle, and deep zones. Chondrocytes were surrounded by a pericellular matrix and were assumed spherical prior to tissue swelling and load application. Material properties of the chondrocytes, pericellular matrix, and extracellular matrix were obtained from the literature. The loading protocol included a free swelling step followed by a stress-relaxation step. Results from traditional isotropic and transversely isotropic biphasic models were used for comparison with predictions from the current model. In the superficial zone, cell shapes changed from rounded to elliptic after free swelling. The stresses and strains as well as fluid flow in cells were greatly affected by the modulus of the collagen network. The fixed charge density of the chondrocytes, pericellular matrix, and extracellular matrix primarily affected the aspect ratios (height/width) and the solid matrix stresses of cells. The mechanical responses of the cells were strongly location and time dependent. The current model highlights that the collagen orientation and the depth-dependent negative fixed charge densities of articular cartilage have a great effect in modulating the mechanical environment in the vicinity of chondrocytes, and it provides an important improvement over earlier models in describing the possible pathways from loading of articular cartilage to the mechanical and biological responses of chondrocytes.

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