Dynamic Culture

Cellular stress can arise from mechanical forces acting on the cells, with excessive forces causing rupture of the cell membrane and ultimately cell death. However, below this upper limit, mechanical stress is an important environmental stimulus, defined by physical forces that have a magnitude and most importantly a direction, so called vectors. The most basic forms are compression, tension, bending and torsion. More complex forms include hydrostatic pressure and shear stress.

Mechanical forces are an essential component of the cellular microenvironment, which in vivo is gradually changing its physicochemical properties. This dynamic nature is closely related to tissue/organ development, regeneration, wound healing, and disease progression. Mechanical stress can guide the cells during differentiation or proliferation and trigger secretion of different extracellular matrix (ECM) molecules. Forces also help cells to organize spatially, to align like we see in muscle and tendon or build layered structures e.g. in skin. Therefore, in vitro platforms that mirror dynamic in vivo signalling may improve the understanding of essential biological processes and help to advance tissue engineering and regenerative medicine. Therefore, unlike in static culture conditions, the use of bioreactors for dynamic culture provides the physical cues and an improved nutrient supply which bears the potential to achieve a more organ- or tissue-specific environment for the cells.

Types of mechanical forces acting on a cell; blue arrows indicate the direction of the force.

Bioreactors come in different shapes and sizes, all depending on the intended application. Very common types are mixing reactors (e.g. stirred tank bioreactors (STBR),  vertical wheel, wave™ bioreactor) and perfusion bioreactors (e.g. hollow-fibre). Mixing bioreactors provide homogenous distribution of nutrient, oxygen as well as cellular by-products during cultivation via stirring or oscillating and rocking components, while keeping the cells in suspension in the vessel. Compared to mixing bioreactors, in perfusion bioreactors a flow of cell culture medium is applied upon the cell population to distribute the oxygen and nutrients throughout the entire bioreactor vessel. Furthermore, it has also been used to apply controlled shear stress to induce differentiation or enhance release of by-products such as extracellular vesicles.

Some examples of bioreactors; mixing direction is indicated by yellow arrows