Because a true microgravity environment results in a reduction of mechanical forces on the human body, possibly at each level of physiological organization, we have investigated the effects of applying a stimulus in the form of fluid-induced shear stress to regenerating articular cartilage cultured in an environment hypothesized to simulate aspects of microgravity. Significant alterations to the NASA-designed rotating wall vessel were made to create a unique bioreactor specifically designed for this study. This distinctive reactor not only allowed us to apply fluid-induced shear stress to tissue constructs, it allowed for control of its magnitude, and for independent control of distinct microgravity conditions.;Simulated microgravity conditions were found to decrease the concentration of cells and extracellular matrix components as has been observed in true microgravity. Our results provide support that rotational rate in horizontally rotating cultures affects cellular events and may have a direct relation in the simulation of aspects of microgravity. Negligible to low levels of shear stress had no significant effect on tissue cellularity until a higher level of shear was applied, suggesting a possible threshold value. The application of shear stress was found to slightly decrease glycosaminoglycan levels. We have uncovered evidence that the effects of fluid-induced shear stress and simulated microgravity interact to affect cell numbers and extracellular matrix production in regenerating cartilage tissue. Results of the interaction studies, that are the first of their kind, showed varying response due to shear depending on the condition of microgravity, and varying response due to microgravity conditions depending on the level of shear.
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