The Role of Matrix Composition and Age in Solute Diffusion within Articular Cartilage

Abstract

Solute diffusion is critical to maintenance of cellular function and matrix integrity in articular cartilage. Nutrient deficiency due to transport limitations is thought to be one of the causes of the pathological degeneration of the cartilage tissue. Thus, a study of diffusion within cartilage will lead to a better understanding of the causes of cartilage degeneration. To accurately estimate diffusion coefficients in cartilage and other hydrated medium, we developed a finite-element based method, the Direct Diffusion Simulation Parameter Estimation method (DDSPE), to be used for quantitative determination of solute diffusivities from Fluorescence Recovery After Photobleaching data. Analyses of simulated and experimental FRAP data demonstrated that this method was more accurate than existing analytical methods, including having a low sensitivity to variations in the spot radius. Subsequently, the roles of extracellular matrix (ECM) composition and tissue orientation in solute diffusion within immature bovine cartilage were explored. Diffusivities were measured through the cartilage depth and in two different orientations (radial and transverse). Diffusivities were then correlated with ECM components. Matrix water content was found to be the best predictor of solute diffusion rates in immature cartilage. Although no specific experiments were done to measure the effect of structure, our results suggested that matrix structure did indeed modulate transport. Diffusional anisotropy, defined as the ratio of the diffusivities in both orientations, was observed to be significant in all the immature cartilage zones. As a consequence, the differences in solute diffusion between immature and mature bovine cartilage were investigated. Diffusion rates and diffusional anisotropy decreased in the mature cartilage superficial zone. The decrease in diffusivities observed in mature cartilage suggests that there may be a reduction in nutrient and growth factor supply to the cells. Nevertheless, healthy adult cartilage can still maintain its normal function even with a reduction in solute diffusion rates as nutrient diffusion distances are shorter in mature cartilage. However, any disruption in the mechanical or biological environment could cause an imbalance in tissue homeostasis, which when combined with decreased diffusivities, could trigger matrix degeneration. Thus, decreased diffusivity may be a necessary but not a sufficient prerequisite of matrix degeneration.