On the Permeability and Diffusivity of Articular Cartilage

Date
2020-04-01
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Abstract
Articular cartilage (AC) consists of a fluid-saturated porous proteoglycan matrix, reinforced by collagen fibres. Since AC is avascular, nutrients transport within AC via diffusion, characterized by diffusivity, and via fluid flow, characterised by permeability. When AC degenerates, diffusivity and permeability are altered, impacting nutrient transport. This work investigates AC diffusivity and permeability, their relationship to one another and to the microstructure in healthy tissues, as a first step towards understanding nutrient transport in degenerated tissues. AC properties are anisotropic, due to the collagen fibre organisation, and heterogeneous, due to the zonal variation of AC composition and architecture. Therefore, permeability and diffusivity are treated as tensors, and are studied as a function of tissue depth. Current permeability and diffusivity models in AC are at different levels: while advanced anisotropic large-deformation models of permeability exist, virtually no model exists for diffusivity. The works consist of two parts: Part I. We propose a multi-scale permeability model under large deformations, accounting for the distortion at the fibre level and for fibre reorientation. When applying compressive strain along the tissue’s depth, the model predicts an increase in the ratio of axial to transverse permeability, which is in agreement with the literature. Part II. We study the relationship between diffusivity and permeability in AC. We propose a tensor representation of diffusivity in terms of permeability, based on the effective medium approach, and accounting for the anisotropy induced by the fibres. The model captures the diffusivity magnitude of uncharged spherical molecules of various sizes and the diffusivity anisotropy of linear molecules. We then propose and validate a direct method for quantifying diffusivity tensor from Fluorescence Recovery After Photobleaching experiments. This method is then used to quantify the diffusivity of 3 kDa and 500 kDa dextran molecules across AC depth. Diffusivity measurements are then analysed using the diffusivity-permeability model, through which the role of fibre alignment in diffusivity anisotropy is highlighted. We then describe some attempts at testing AC transverse permeability using microfluidics-based techniques and the associated challenges. Finally, we highlight some limitations of our work and possibilities for future developments.
Description
Keywords
Articular Cartilage, Molecular Diffusion, Transport, Permeability, Diffusivity, Fibrous Tissues
Citation
Hashlamoun, K. (2020). On the Permeability and Diffusivity of Articular Cartilagethesis (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.