Date of Award
Doctor of Philosophy
Chemical and Biological Engineering
Carole A. Heath
A semi-continuous perfusion system has been designed and constructed to deliver physiological levels of hydrostatic pressure to regenerating cell/polymer constructs of articular cartilage over the long term (weeks to months). Prior to being transferred to the pressurized system, equine articular chondrocytes were dynamically seeded onto nonwoven meshes of polyglycolic acid which provide the cells with a three-dimensional growth environment similar to that found in vivo. When applied in an intermittent manner, physiological pressurization at 500 psi was found to stimulate articular chondrocytes to produce regenerated constructs with greater concentrations of sulfated glycosaminoglycan compared to control (unpressurized) constructs, while the concentration of collagen was not significantly different between pressurized and control samples. Foal articular chondrocytes were found to produce significantly greater amounts of the extracellular matrix (sulfated glycosaminoglycan and collagen) than chondrocytes isolated from adult horses (greater than two years of age) at similar pressure levels. Increasing the level of physiological intermittent pressure from 500 psi to 1000 psi was found to further increase the concentration of sulfated glycosaminoglycan in regenerated constructs and, for the first time, was shown to significantly increase collagen concentrations above control samples, suggesting that a minimum level of dynamic force may be needed to stimulate collagen production. By combining pressurized and stirred culture environments, tissue constructs were developed which had greater concentrations of the extracellular matrix than constructs regenerated in single culture environments and masses greater than those previously developed in stagnant (minimum medium perfusion) pressurized cultures. A correlation was noted between the compressive modulus, which is a measure of the strength of a regenerated construct, and the concentration of sulfated glycosaminoglycan in constructs cultured mostly in a pressurized environment. The fact that this correlation has not been shown in control samples or in samples cultured mostly in mixed cultures, suggests that intermittent pressurization may influence the structural arrangement of the extracellular matrix. This form of dynamic loading creates regenerated tissue which is more mechanically stable than constructs cultured in the absence of forces similar to those experienced in the native environment.
Digital Repository @ Iowa State University, http://lib.dr.iastate.edu/
Scott Edward Carver
Carver, Scott Edward, "The effects of physiological levels of intermittent pressure on the development of articular cartilage in vitro " (1998). Retrospective Theses and Dissertations. 11846.