Importance of Collagen Orientation and Depth-Dependent Fixed Charge Densities of Cartilage on Mechanical Behavior of Chondrocytes

Abstract

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.

Multiscale cartilage biomechanics: technical challenges in realizing a high-throughput modelling and simulation workflow

“…Yet, an understanding of multi-modal loading and overall deformations of individual cells and/or populations of cells may be necessary. Metrics such as cell height and width, aspect ratio and volume (undeformed and deformed) have commonly been used for describing experimental data [11] and simulation results [56], with the intention to associate cell mechanics with cell damage and mechanical stimuli. Such descriptors, however, are not readily available in raw simulation results, and automated procedures are necessary if these variables need to be evaluated for hundreds of cells and for a large number of simulation conditions.…”

The Influence of Cell-Matrix Attachment and Matrix Development on the Micromechanical Environment of the Chondrocyte in Tissue-Engineered Cartilage

“…28 Besides these agreements, it is also worth mentioning that the constitutive material model for native ECM has previously been validated and used for studies at both the macroscopic tissue 21,22,30 and the microscopic cell level. 24,[31][32][33][34][35][36] The different macroscopic and microscopic depthdependent strain fields between native cartilage and TE constructs may have implications for the mechano-response of the chondrocytes to mechanical stimulation. Cells may have adapted over time to particular in vivo environments, which may or may not resemble those that are exposed to in TE constructs, depending on the location where they end up after seeding.…”

The effect of tissue-engineered cartilage biomechanical and biochemical properties on its post-implantation mechanical behavior

“…The functional significance of the specific physiological depth-dependent collagen structure in native tissue (with vertical fibers in the deep zone and horizontal fibers in the superficial zone) is well emphasized in the literature (Korhonen et al 2002;Owen and Wayne 2006;Wilson et al 2007;Korhonen et al 2008;Shirazi and ShiraziAdl 2008;. Vertical fibrils in the deep zone resist swelling (Wilson et al 2006b) and protects the solid matrix against large strains at the subchondral junction .…”