From the Lab-on-a-Chip to the Organ-on-a-Chip

Dear Colleagues,

Human health is of great importance to all of us; yet, a great extent of the present understanding of human physiology, that is, the function of organs, tissues, and cells in an organism, is based on the use of cell lines in a 2D monolayer culture. There are countless cell lines available from various origins, such as human blood, different organs, and even pathological tissues, such as tumors.

Although of immense value in past research, conventional 2D cell cultures are strongly limited in recreating the complex interactions of different cell types, tissues and organs within higher organisms (e.g., vertebrates). The communication of cells through direct cell–cell contact, and by the release of chemokines, are also skewed in 2D cell culture since 3D structures are missing and the ratio of cells to the volume of surrounding fluid (media) is non-physiological. Furthermore, tissue-specific parameters, such as pH, pO₂, extracellular matrix composition, or the presence of mechanical forces, are underrepresented in monolayer cell cultures.

Thus, the translation of the data gained in conventional cell cultures into complex organisms is hampered, a disadvantage that is apparent in many fields, such as regenerative medicine or toxicology. To compensate for these shortcomings, animal experiments are widely used, especially in risk assessment or the testing of chemicals and novel drugs. Here, animal testing provides some information on drug activity; however, in any case, drugs are then tested in subsequent phases (clinical trials) on human probands.

On the other hand, the culture of cells outside the human body is challenging and requires specific knowledge regarding the accompanying limitations. While it is the standard to grow cells in 2D monolayer cultures, which only poorly resemble physiological situations, there have been many attempts to cultivate them in 3D to improve their biological relevance. The further transition from 3D cell culture models to organ-on-a-chip (OoC) systems allows for the recreation of a physiological environment that resembles the parameters of the tissues of interest and also allows the co-culture of different tissue-specific cell types in 2D or 3D.

Recent advances in Microelectromechanical Systems (MEMS) enable the construction of OoCs with structures in the range of nano- and micrometers. Various materials can be utilized—from silica to ceramics, glass, metals or different polymers (some with refractory properties similar to glass). Since cells require a water-based environment, microfluidics are especially suitable for their cultivation. Microfluidics offers precise control and manipulation of fluids with many advantages over classic bioreactor systems. It is possible to design growth chambers and flow channels in practically any size and shape, while the volumes of reagents, samples and cell organoids are comparably small. The risk of contamination can be reduced, for example, by utilizing disposable chips. Due to a change in surface-to-volume ratios, the speed of chemical reactions is increased when compared to the macro-scale, resulting in enhanced heat transfer and lower energy requirements.

Advances in miniaturization and manufacturing processes have led to the availability of a plethora of cheap sensors that allow for easy control, thus leading to the rapid automatization of OoCs.

We are facing the successful marriage between cell biology and microfluidic chips, leading to the infancy of OoC. We are sure that the importance of OoC technology will lead to the successful development of various OoCs and their interconnection in one platform, also termed body-on-a-chip.

We anticipate that the further development and standardization of OoCs will result in faster and cheaper drug development, without the need of using laboratory animals for testing. Further OoC use will facilitate a more fundamental understanding of cell function and cell communication. OoC technology may be suitable, not only for the study of human cells, but also for other animal cells, prokaryotes, or even viruses.

Let us share the latest developments of OoC with a series of original high-quality articles and reviews in this Special Issue of Genes.

Prof. Dr. Rimantas Kodzius
Dr. Ing. Frank Schulze
Prof. Dr. Marlon R. Schneider
Dr. Xinghua Gao
Guest Editors

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