Multi-scale physico-chemical phenomena in articular cartilage and subchondral bone

Abstract

Articular cartilage and its connecting subchondral bone plate are main compartments that play an important role in proper mechanical functioning of diarthrodial joints. However, in ageing and osteoarthritis structural changes propagate in these tissues, which impairs them for proper functioning. One way to characterize the structural alterations during different stages of degeneration and disease is to perform solute transport tests in an experimental set-up and quantify the parameters such as diffusivity and permeability that represent the quality of the tissue. Therefore, common imaging techniques to investigate diffusion across cartilage have been reviewed and suggestions to select appropriate tools to determine diffusion parameters were made. The primary aim of this thesis is to setup a set of experiments that can capture the transport properties of cartilage and its underlying bone. To this end we designed experiments that used contrast-enhanced micro-computed tomography to measure diffusion through cartilage and subchondral bone and applied computational models of these experiments to quantify the physical parameters such as diffusivity and permeability of the tissues concerned. The individual role of the bath osmolality, concentration and solute’s charge on the diffusion in articular cartilage was successfully studied and solute’s charge was identified as the dominant factor. Biphasic-solute and multiphasic finite element models were subsequently developed to precisely simulate the transport of neutral and charged solutes in various cartilage zones, respectively. As the cartilage-bone interface experiences morphological alterations after joint degeneration and during progression of osteoarthritis, characterization of the transport properties of the interface becomes of paramount importance. Therefore, experiments based on contrast-enhanced micro-computed tomography were first conducted and a correlation was found between the extent of diffusion and the micro-architecture of the subchondral bone plate and articular cartilage. Multi-zone biphasic-solute finite element models then assisted in determination of diffusion coefficients in different cartilage layers and the subchondral bone plate. To identify the pathways between cartilage and bone responsible for transport, focused-ion-beam scanning electron microscopy imaging was employed. Using the 3D data of the pore structure at the osteochondral interface and with the aid of advanced pore-network modeling, the diffusive and permeability attributes of the extracellular matrices were successfully determined. The next theme of this thesis was to assess the effects of collagen fibril conformation under different environmental osmotic pressure on advanced non-enzymatic glycation, a process, responsible for cartilage deterioration during ageing. Sugars were added under different external bath osmotic pressures to study the glycation process when collagen fibrils are either stretched or shrunk. Using micro-indentation, biochemical assays, contrast-enhanced micro-computed tomography and cartilage surface colorimetry, the stretching of the collagen fibrils was found to minimize the degenerative effects of sugar-induced glycation. The author believes that the current findings contribute to solve the yet-challenging physico-chemical problems involved in the cartilage and its related joint disease. The current work will lead to new techniques that aim to not only understand the fundamental physico-chemical aspects of cartilage, but also might suggest methods for efficient delivery of drugs into the cartilage tissue and visualizing agents that could better follow and diagnose joint disease.