Monitoring and real-time control of tissue engineering systems

Tissue engineering (TE) systems (TESs) are devices and accessories that enable the in vitro culture of engineered tissues for regenerative medical, diagnostic, or research purposes and include everything from a simple tissue culture plate to complex TE bioreactors, and to the defined protocols used to effect tissue growth. Monitoring and control in TE bioreactors is important for several reasons. (1) To ensure homeostasis selected parameter. In many cases, for example, temperature, the monitored and controlled variable are the same. In other cases the controlled variable can be used to indirectly manipulate the tissue. (2) To address and possibly overcome the variability intrinsic to the cellular component. This includes adapting to the tissues varying responses to stimuli. Finally, (3) monitoring can be used to identify failures in the TE protocol. Monitoring of a TES can be done at several levels: cellular (e.g., gene expression), tissue (e.g., matrix deposition of mechanical performance), and environmental (e.g., temperature, O2, CO2, pH, nutrient concentrations, and osmotic environment). Control for homeostasis of environmental properties is a fairly mature technology; on the other hand, monitoring of emerging properties of the developing tissue may, at this point, only result in go/no-go decisions for the particular piece of tissue. In many cases, this is because we do not yet know what parameters to adjust to effect a correction. At this point, collecting and compiling as much data from the performance of TES, including the failures, is of paramount importance to advance the field.