Mechanical actuation. The extracellular environment is an essential mediator of cell function and provides not only biochemical but also mechanical cues to influence cell phenotype and behavior. Among various mechanical cues, matrix elasticity has a crucial role in the induction of cellular responses and fate including proliferation, differentiation, migration, adhesion, and maturation. Mechanical properties determine the tissue’s capacity to resist deformation induced by stress, such as compression, elongation, or shear force (Xxxxxxx et al. 2018). Cells and tissues in the body experience varying degrees of mechanical forces, ranging from tensile to compressive forces (Xxxxxx et al. 2007)(Xxxxx et al. 2012). However, careful consideration regarding the duration, frequency, and amplitude of mechanical forces is important to mimic physiological mechanical forces experienced by different cells and tissues in the body. In addition to applied stimuli, cells naturally experience varying degrees of mechanical strain due to their interactions with the extracellular matrix (ECM) proteins. Mechanical actuation can be induced by (indirect) electromechanical stimulation of cells or direct mechanical stimulation. For example, electrical stimulation yields a mechanical contraction in cardiac cells or tissues (Xxxxx et al. 2013)(Xxxxxxxx et al. 2010). Direct mechanical stimulation is performed by applying stretch (Xxxxxxxxxx et al. 2000). Some implementations include both functionalities (Rangarajan, Madden, and Bursac 2014). Careful consideration regarding duration, frequency and amplitude should be applied when mimicking physiological mechanical forces to cells. Hence, in addition to applied stimuli, cells experience a varying degree of mechanical strain due to interactions with the ECM. In this aspect, spatial cues are equally important. Cells have been shown to respond to sensing surface properties on the nano- and microscale which result in phenotypic changes (Xxxxxxx et al. 2013). Engineering tissues for OOC applications requires directing cell growth, orientation and interactions. Mechanical actuation seems to represent a key parameter in the standardization of technologies used in OoC’s, but its implementation is, in analogy with the cells in the body, highly variable. Mechanical strain in the human body ranges typically between a few percent in the tendons and ligaments (2-5%) and in the lung alveoli (4-12%) and can reach up to tens of percent when muscles or skin are stretched (Sch...
