The Emergence of Organ-on-chips for Diseases Studies and Drug Development

Organ-on-chips have recently emerged as microphysiological systems enabling to overcome the limitations of traditional cell culture methods and the use of animal models [1, 2]. They can simulate the functional unit of an organ, account for multi-organ interplay, and facilitate the drug development process and progress in the present knowledge on pathological mechanisms responsible for human illnesses.

Organ-on-chips for Diseases Studies and Drug Development

Organ-on-chip models with details about their involvement in different drug delivery routes and the employed cell lines [reproduced from A. G. Monteduro, S. Rizzato, G. Caragnano, A. Trapani, G. Giannelli and G. Maruccio, Organs-on-chips Technologies: A guide from disease models to opportunities for drug development, Biosensors and Bioelectronics 2023, 231, 115271, http://dx.doi.org/https://doi.org/10.1016/j.bios.2023.115271]

A new frontier of technology: Organ-on-chips

In recent years, organ-on-chips (OOC) have attracted large interest as a new enabling technology to better understand human pathophysiological mechanisms and develop new drug treatments [1, 2]. These microfluidic devices can recapitulate the functional unit of an organ, reproducing the tissue architecture and mechanics of the organ in question. Differently from 2D cultures, organ-on-chips can allow 3D growth and account for cell-cell interactions and can be subjected to mechanical stimuli that mimic those present in vivo, such as the movement of intestinal peristalsis, lung respiration, and heartbeat. Compared to animal models, OOC does not have ethical issues and does not have the problem of limited translatability of results between humans and animals. In addition, sensors can be integrated into OOCs to monitor cell activity, such as cell proliferation, or changes in oxygen concentration or pH that are reflected in cell culture conditions. OOCs are made by microfabrication techniques such as photolithography and soft lithography.[1, 2]

A new tool for drug discovery

The process of identifying a new drug is very long, costly, and partially inefficient. On average, it takes about 15 years, highly specialized personnel is needed, millions of dollars are spent and the success rate in identifying a new drug is very low, less than 5%, resulting in a waste of many resources. OOC microfluidic devices could speed up this process, being faster and better at testing the efficacy of a drug on a target organ and also assessing its toxicity on other organs through which the drug passes [1, 3]. In the search for new orally administered drugs, the compound toxicity on the involved organs can be investigated on the chip, including the effect on the liver where it is metabolized and the kidneys by which it is eliminated [2, 4]. For this purpose, researchers developed multi-organ-on-chip devices, having interconnected compartments for each target organ.

Multi-organs platforms

Multi-organ on-chip (MOC) devices are intended to recapitulate the communication between the various organs to represent the interface of different tissues that make up biological barriers using different closely connected compartments. These models can also contribute to investigating the kinetic and dynamic course of a drug (PK-PD) by monitoring the various responses of multiple organs to pharmaceutical compounds under development. 

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