Principles of analogue and true microgravity bioreactors to tissue engineering

Abstract

Understanding the effects of microgravity per se on cultured cells is greatly advanced by the use of fluid physics and computational fluid dynamics. It is essential that the design and operation of cell culture systems for application in microgravity and microgravity analogue conditions are accompanied by thorough analysis of the physical environment in the context of gravity and fluid properties. This becomes critically important when assessing whether the cells are responding directly to microgravity as opposed to the indirect cell response to environmental (fluid) conditions created by microgravity, such as changes in fluid shear on the cell surface. The development of the rotating wall vessel (RWV) bioreactor systems that reproduce aspects of the microgravity environment was an orderly process of developing and optimizing models through iterative tests and validations. Without this deliberate approach, it would have been difficult to advance our understanding of low gravity and low fluid shear environments and their impact on cellular biology. This innovative approach to cell culture and tissue engineering enabled the development of three-dimensional (3-D) organotypic tissue aggregates that better recapitulate the form and function of the parental tissue in vivo when compared to cells cultured as conventional flat 2-D monolayers. In addition to culture of mammalian cells under low fluid shear stress, the RWV bioreactor has also been used to culture microbial pathogens under conditions of physiological low fluid shear that are relevant to those encountered in the infected host during the natural course of infection. These studies have revealed novel insight into pathogenic mechanisms used by microbes during the infection process, which are not observed during conventional culture.