Bioreactors with hydrostatic pressures imitating physiological environments in intervertebral discs

Intervertebral discs are normally exposed to a variety of loads and stresses but hydrostatic pressure (HP) could be the main biosignal for chondrogenic cell differentiation and maintenance of this tissue. Although there are simple approaches to intermittently expose cell cultures to HP in separate material testing devices, utilization of biomimetic bioreactors aiming to provide in vitro conditions mimicking those found in vivo, attracts special attention. However, design of such bioreactors is complex due to the requirement of high HP magnitudes (up to 3 MPa) applied in different regimes mimicking pressures arising in intervertebral disc during normal daily activities. Furthermore, efficient mass transfer has to be facilitated to cells within 3D scaffolds, and the engineering challenges include avoidance or removal of gas bubbles in the culture medium before pressurization as well as selection of appropriate, biocompatible construction materials and maintenance of sterility during cultivation. Here, we review approaches to induce HP in 2D and 3D cell cultures categorized into 5 groups: (I) discontinuous systems with direct pressurization of the cultivation medium by a piston, (II) discontinuous systems with indirect pressurization by a compression fluid, (III) continuous systems with direct pressurization of the cultivation medium, static culture, (IV) continuous systems with culture perfusion, and (V) systems applying HP in conjunction with other physical signals. Although the complexity is increasing as additional features are added to the systems, the need to understand HP effects on cells and tissues in a physiologically relevant, yet precisely controlled, environment together with current technological advancements are leading towards innovative bioreactor solutions.