Bioreactor engineering: Regenerating the dynamic cell microenvironment

The replacement of the "flat biology" of the Petri dish with three-dimensional (3D) cell cultures has shown to narrow the gap between cell behaviours and function in vitro and at the physiological settings. A fundamental challenge to realise the potential of the 3D cell culture is the design and application of "smart" bioreactor systems. These systems should provide homogenous mass transport into the internal volume of the cultured cell constructs as well as to efficiently propagate physical and mechanical stimuli. Herein, we describe the design principles of various bioreactors, starting with the conventional spinner flasks, the rotary wall vessels and up to the latest perfusion vessels. In particular, the key role of perfusion bioreactors in regenerating the dynamic 3D cell microenvironment is demonstrated by providing a few successful examples of engineering thick functional tissues, such as the cardiac muscle tissue. In closing this chapter, we envision future innovations in bioreactors.