Advances in Micro-Bioreactor Design for Organ Cell Studies

The engineering design of microbioreactors (MBRs) and Organ-on-Chips (OoCs) has advanced considerably in recent years [...]

consists of three different parts, containing two microfluidic channels and a porous membrane sandwiched in between. In contrast to many other systems, this device does not need an additional coating to allow endothelial cell (EC) growth, as the primary ECs used produce their own basement membrane. The ECs in their device showed in vivo-like behavior under flow conditions. These results suggest that the new device can be used for research on molecular requirements and conditions and the mechanism of extravasation and its inhibition.
Toh and colleagues [9] have developed a microfluidic-based culture chip to simulate cancer cell migration and invasion across the basement membrane. In this microfluidic chip, a three-dimensional (3D) microenvironment is engineered to culture metastatic breast cancer cells in a three-tumor model. The chip is useful for drug screening due to its potential to monitor the behavior of cancer cell motility, and, therefore, metastasis, in the presence of anti-cancer drugs.
Investigating effects of drug compounds on organ cells in in vitro microfluidic models has been mentioned recurrently to fill the need in the pharma industry for more efficient drug testing. In a study by Christoffersson and colleagues [10], a 3D model with cells arranged in spheroids is shown to be a valuable tool to improve physiologically relevant drug screening. In this article, it is shown how the number of cells growing out from human-induced pluripotent stem cell (hiPSC)-derived cardiac spheroids can be quantified to serve as an indicator of a drug's effect on spheroids captured in a microfluidic device.
Freyer and colleagues [11] demonstrate another approach with the same purpose with liver cells. They investigated the response of primary human liver cells to toxic drug exposure in a miniaturized hollow-fiber-based bioreactor. The results validate the suitability of the microscale 3D liver construct to detect hepatotoxic effects of drugs in a perfused human in vitro culture platform.
In another MBR setup, Wrzesinski and Fey [12] carry out an in-depth study of hepatocytes metabolism. They describe basic principles and how they are regulated so that they can be taken into consideration when microbioreactors are designed. They provide evidence that one of these basic principles is hypoxia, a natural consequence of multicellular structures grown in microgravity cultures.
Aspects of fluid dynamics in MBRs are addressed by Tajsoleiman et al. [13]. Due to the sensitivity of mammalian cell cultures, understanding the influence of operating conditions during a tissue generation procedure is crucial. In this regard, a detailed study of scaffold-based cell culture under a perfusion flow is presented with the aid of mathematical modelling and computational fluid dynamics (CFD). The simulation setup provides the possibility of predicting cell culture behavior under various operating conditions and scaffold designs.
Another important aspect of MBR design is oxygen distribution. Fernandez et al. [14] demonstrate the use of oxygen sensors to measure the oxygen consumption rate of several variants during the conversion of styrene (substrate) to 1-phenylethanediol (product). The oxygen consumption rate allowed for distinguishing the endogenous respiration of the cell host from the oxygen consumed in the reaction. Furthermore, it was possible to identify the higher activity and different reaction rate of two variants relative to the wild-type NDO.
All together, these nine contributions reflect state-of-the-art aspects of MBR design and highlight the inherent potential and strengths of the concept of MBRs for organ cell studies.

Conflicts of Interest:
The author declares no conflict of interest.