The Mechanical Behaviour of Chondrocytes Predicted with a Micro-structural Model of Articular Cartilage

Abstract

The integrity of articular cartilage depends on the proper functioning and mechanical stimulation of chondrocytes, the cells that synthesize extracellular matrix and maintain tissue health. The biosynthetic activity of chondrocytes is influenced by genetic factors, environmental influences, extracellular matrix composition, and mechanical factors. The mechanical environment of chondrocytes is believed to be an important determinant for joint health, and chondrocyte deformation in response to mechanical loading is speculated to be an important regulator of metabolic activity. In previous studies of chondrocyte deformation, articular cartilage was described as a biphasic material consisting of a homogeneous, isotropic, linearly elastic solid phase, and an inviscid fluid phase. However, articular cartilage is known to be anisotropic and inhomogeneous across its depth. Therefore, isotropic and homogeneous models cannot make appropriate predictions for tissue and cell stresses and strains. Here, we modelled articular cartilage as a transversely isotropic, inhomogeneous (TI) material in which the anisotropy and inhomogeneity arose naturally from the microstructure of the depth-dependent collagen fibril orientation and volumetric fraction, as well as the chondrocyte shape and volumetric fraction. The purpose of this study was to analyse the deformation behaviour of chondrocytes using the TI model of articular cartilage. In order to evaluate our model against experimental results, we simulated indentation and unconfined compression tests for nominal compressions of 15%. Chondrocyte deformations were analysed as a function of location within the tissue. The TI model predicted a non-uniform behaviour across tissue depth: in indentation testing, cell height decreased by 43% in the superficial zone and between 11 and 29% in the deep zone. In unconfined compression testing, cell height decreased by 32% in the superficial zone, 25% in the middle, and 18% in the deep zones. This predicted non-uniformity is in agreement with experimental studies. The novelty of this study is the use of a cartilage material model accounting for the intrinsic inhomogeneity and anisotropy of cartilage caused by its microstructure.

Computational investigation of in situ chondrocyte deformation and actin cytoskeleton remodelling under physiological loading

“…This was determined by considering that the volume fraction of chondrocytes in cartilage tissue varies from 1-10% [40,46], and cellularity decreases with tissue depth from 150 × 10 6 cells/cm 3 at the surface to 50 × 10 6 cells/cm 3 at 500 μm below the surface [47]. Additionally, the ratio of cell volume to ECM volume in the current study is comparable to previous finite element models incorporating chondrocytes embedded in an ECM [15,17,18,48].…”

“…Moo et al [18] modelled the response of embedded chondrocytes in cartilage tissue to confined compression using a biphasic model to represent the cell, with the ECM assumed to be isotropic. A transversely isotropic model for cartilage, surrounding a passive non-contractile isotropic elastic chondrocyte, has been employed to analyse cell deformation during compression [17]. A viscoelastic fibre-reinforced constitutive model based on a convex strain-energy function has been used to model collagen fibre and cartilage deformation during indentation, without explicitly modelling chondrocytes embedded in the tissue [33,87].…”

“…Chondrocytes have been commonly modelled as biphasic and isotropic in multi-scale models when simulating their response to deformation [15][16][17][18]. In addition, viscoelastic models have been employed to simulate chondrocyte behaviour during single cell micropipette aspiration [19,20] and shear experiments [21].…”

Structural and Compositional Changes in Peri- and Extracellular Matrix of Osteoarthritic Cartilage Modulate Chondrocyte Morphology

“…It is generally accepted that the superficial layers of cartilage strongly modulate the mechanical response of cartilage and cellular deformations. 15,21,33,34 Therefore, minor degradation and disorganization or complete erosion of the superficial zone during the progression of OA may further accelerate disease progression due to the harmful alterations in the mechanical environment of chondrocytes, stress/strain states in the tissue, and cartilage mechanotransduction.…”

A poroplastic model of structural reorganisation in porous media of biomechanical interest

“…Moreover, they may provide indications about the mechanical conditions regulating the health of tissues; for example, in the case of articular cartilage, the health of the tissue depends on the mechanical environment in which chondrocytes live (the chondrocytes are the cells that synthesise extracellular matrix, cf. [54,55,73,74] and references therein). Finally, the mathematical model presented in this paper could be generalised to include also growth [45] and damage [23,24,41].…”