Interstitial solute transport in articular cartilage and the role of dynamic compression
Articular cartilage plays important roles in weight-bearing, lubrication, and load distribution in articulating joints. The tissue is mostly extracellular matrix (>90% by volume) that is synthesized and remodeled by cells (chondrocytes) embedded within. Adult articular cartilage has no blood or lymph supply; therefore solute diffusion and convection through the mechanically functional extracellular matrix are essential for cell nutrition, waste removal, matrix remodeling, and intercellular signaling. Chondrocytes exhibit specific biological responses to cartilage mechanical compression. Under physiological loading, chondrocyte-mediated matrix synthesis rates tend to decrease with static compression, but increase with dynamic loading and associated fluid flows. It was hypothesized that alterations in solute transport may mediate this mechanotransduction. Goals were to apply novel tools for measurement of solute transport in mechanically loaded articular cartilage, with particular attention to effects of dynamic compression. Initial studies explored relationships among solute diffusivities, matrix mechanical properties, and matrix density in compressed articular cartilage. Diffusion coefficients were measured using confocal microscopy measurements of solute desorption from cartilage explants. Examined solutes included fluorophores and fluorescently-labeled dextrans of various charges. Diffusivities tended to decrease with increasing matrix density and most interestingly, exhibited a significant negative correlation with axial matrix stiffness. Results suggest that in vivo interstitial diffusion measurement may be used for clinical identification of focal mechanical weakening of cartilage. Furthermore, monitoring of mechanical properties of engineered cartilage constructs in vitro may provide information regarding cell transport environments during matrix accumulation. Novel experimental methods were also used for quantification of solute convection during dynamic compression of cartilage. Solute convection coefficients measured within cartilage disks during radially unconfined axial compression and release indicated positive effects of fluid flow on transport for several solutes. However, not all solutes were affected to the same extent. A range of compression amplitudes and frequencies were then applied to determine an optimum regime for transport of a fluorescent glucose analog. Solute desorption was increased by 37% (over static compression) under a dynamic compression protocols similar to those previously found to stimulate chondrocyte metabolism. Methods and results may have application in optimized mechanical conditioning of cartilage constructs in tissue engineering applications. Findings demonstrate that dynamic compression and associated fluid flows can enhance transport of a wide range of molecules in cartilage. Mechanical loading conditions that are known to stimulate cell-mediated matrix synthesis appear to optimize the transport of solutes such as glucose. Results strongly support the hypothesis that alterations in solute transport mediate the cell response to cartilage compression. Methods and results may therefore aid in improving understanding of cartilage biomechanics and physiology, and contribute to improved strategies for tissue engineering and cartilage repair.
Section de génie mécanique
Faculté des sciences et techniques de l'ingénieur
Institut de génie biomédical
Jury: Mauro Alini, Jacques Giovanola, Jukka Jurvelin, Melody Swartz
Public defense: 2005-12-19
Record created on 2005-11-28, modified on 2016-08-08