Organ-on-a-chip systems: translating concept into practice

This virtual issue on “Organ-on-a-chip systems: translating concept into practice” continues an assessment of this emerging technology discussed initially as “Advances in organ-, body-, and disease-on-a-chip systems” in Lab on a Chip (DOI: 10.1039/C8LC90089B). The organ-on-chip field has begun to mature with many small companies developing this technology and widespread testing in pharmaceutical and cosmetic firms. The technology is still emerging but recent advances have moved it from conceptual development to application to specific problems. This process is revealing the challenges in the application of these techniques to practical problems and potential solutions to these challenges. The purpose of this collection is to provide examples of how this emerging technology is being applied to a wide range of practical problems.

Within this group of papers is a subgroup organized by Kristin Fabre, Terry R. Van Vleet and others on microphysiological systems (MPS) largely reflecting an industrial perspective on MPS. Fabre et al. (DOI: 10.1039/C9LC01168D) provide an important perspective on these papers, which is followed by four tutorial reviews (DOI: 10.1039/C9LC00962K, DOI: 10.1039/C9LC00857H, DOI: 10.1039/C9LC00519F and DOI: 10.1039/C9LC00492K) and three critical reviews (DOI: 10.1039/C9LC01107B, DOI: 10.1039/C9LC00925F and DOI: 10.1039/C9LC00768G). These papers together provide an excellent perspective on the potential implementation and impact of MPS on drug development, both overall and in other cases focused on specific organs: the skin, lungs, GI tract, kidney and liver. These studies provide the reader with an excellent introduction to this technology and its role in improving drug development.

The papers based on specific research projects address questions in the further development of this novel technology and applications from a single organ to ultimately multi-organ models. Many of these papers focus on advances of the underlying technology. Schurdak et al. (DOI: 10.1039/C9LC01047E) describe a MPS database allowing investigators to share MPS data and ultimately to design better MPS disease models and facilitate potential integration of computational models with data generated from MPS models. Winkler et al. (DOI: 10.1039/D0LC00009D) discuss a low cost MPS using a tape-based barrier-on-a-chip to model the small intestine. Busche et al. (DOI: 10.1039/D0LC00357C) describe a continuously perfused 24 chamber microplate using a novel technique to construct a liver mimic using primary hepatocytes and liver endothelial cells. Hou et al. (DOI: 10.1039/D0LC00288G) discuss an integrated array chip to facilitate a high throughput system to screen drugs for a two organ model (liver–tumor). Ong et al. (DOI: 10.1039/C9LC00160C) describe a modular multi-organ system as a platform to customize models with different physiological systemic interactions. Wong and Simmons (DOI: 10.1039/C8LC01321G) describe a novel microscale system to determine the permeability of barrier tissues. Zakharova et al. (DOI: 10.1039/D0LC00399A) describe a multiplex system to evaluate up to eight parallel systems which they illustrate by testing blood brain barrier models for permeability. These are all technological improvements that may impact the construction of MPS systems and their application to drug development.

Other studies focus on models with an emphasis on biological responses. In some cases the model is for a single tissue. Rothbauer et al. (DOI: 10.1039/C9LC01097A) describe a synovium-on-a-chip and the response to the application of systemic stress factors. Lugo-Cintrón et al. (DOI: 10.1039/D0LC00099J) form a microscale 3D model of breast cancer to determine the effects of microenvironmental cues on lymphatic vessel biology. Mathur et al. (DOI: 10.1039/C9LC00469F) study thromboinflammation using a personalized vessel-on-a-chip model. Jeong et al. (DOI: 10.1039/C9LC00958B) use a 3D lung cancer model to investigate the effect of exosome delivery of microRNAs. Other multi-organ models focus on systems intended to evaluate the potential response of the body to drugs or chemicals. Pires de Mello et al. (DOI: 10.1039/C9LC00861F) describe a PBPK guided human multi-organ microscale system (liver, heart and skin) to determine the efficacy and toxicity of four different drugs that were topically administered. Arakawa et al. (DOI: 10.1039/C9LC00884E) used a two organ (entero–hepatic) model to gain insight into the metabolism of triazolam and extrapolate their model to predict human response.

This group of papers provides an excellent introduction to how these systems may improve drug development and human health. Indeed this technology is now being applied to critical problems such as evaluation of potential drugs and drug combinations to treat Covid-19. This technology is well positioned to speed drug development to emerging diseases by providing a human relevant model for preclinical studies and also for evaluating both the efficacy and toxicity of combinations of existing, approved drugs which may be deployed quickly. This technology is still growing quickly and we expect it to have a significant impact in making more drugs available to humans at a reduced cost.

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