Abstract
Micro and small bioreactors are well described for use in bioprocess development in pre-production manufacture, using ultra-scale down and microfluidic methodology. However, the use of bioreactors to understand normal and pathophysiology by definition must be very different, and the constraints of the physiological environment influence such bioreactor design. This review considers the key elements necessary to enable bioreactors to address three main areas associated with biological systems. All entail recreation of the in vivo cell niche as faithfully as possible, so that they may be used to study molecular and cellular changes in normal physiology, with a view to creating tissue-engineered grafts for clinical use; understanding the pathophysiology of disease at the molecular level; defining possible therapeutic targets; and enabling appropriate pharmaceutical testing on a truly representative organoid, thus enabling better drug design, and simultaneously creating the potential to reduce the numbers of animals in research. The premise explored is that not only cellular signalling cues, but also mechano-transduction from mechanical cues, play an important role.
Highlights
Bioreactors are used in three ways: to enable, in vitro, a mimic of the state in which cells exist in vivo so as to understand normal cell and molecular physiology; to expand cells for potential clinical use, for example in gene and cell therapies, or to mimic a pathological state in order to study the pathophysiology; and to establish new therapeutic targets and test potential new treatments in a more realistic setting than simple in vitro conventional culture
Burk et al [18], using decellularised tendons reseeded with mesenchymal stromal cells, applied mechanical stimulation with a cyclic-strain bioreactor
Our own group has produced a bioartificial liver machine (BAL) on human scale based on a fluidised bed bioreactor design, which maximises mass transfer (UCLBAL), and tested it in a porcine model of acute liver failure [50,52,53]
Summary
Bioreactors are used in three ways: to enable, in vitro, a mimic of the state in which cells exist in vivo so as to understand normal cell and molecular physiology; to expand cells for potential clinical use, for example in gene and cell therapies, or to mimic a pathological state in order to study the pathophysiology; and to establish new therapeutic targets and test potential new treatments in a more realistic setting than simple in vitro conventional culture. Some examples from biology include the performance of blood vessels depending on their role; for example, the make-up of a vein usually delivering low pressure flow at low shear that is responsible for flow but for heat dissipation, compared with an artery responsible for high flows, at much higher pressures, especially close to the heart, which are designed to have thicker musculature in vessel walls and to be more elastic to deal with greater pressures and pulsatile flow; these tissue structures are often anisotropic To model these in a bioreactor, the correct cell type and the mechanical structures capable of delivering the function is necessary. These are not really mimics of any system in the body
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