Microfluidic-Based Multi-Organ Platforms for Drug Discovery

Abstract

Development of predictive multi-organ models before implementing costly clinical trials is central for screening the toxicity, efficacy, and side effects of new therapeutic agents. Despite significant efforts that have been recently made to develop biomimetic in vitro tissue models, the clinical application of such platforms is still far from reality. Recent advances in physiologically-based pharmacokinetic and pharmacodynamic (PBPK-PD) modeling, micro- and nanotechnology, and in silico modeling have enabled single- and multi-organ platforms for investigation of new chemical agents and tissue-tissue interactions. This review provides an overview of the principles of designing microfluidic-based organ-on-chip models for drug testing and highlights current state-of-the-art in developing predictive multi-organ models for studying the cross-talk of interconnected organs. We further discuss the challenges associated with establishing a predictive body-on-chip (BOC) model such as the scaling, cell types, the common medium, and principles of the study design for characterizing the interaction of drugs with multiple targets.

Organ‐On‐A‐Chip Platforms: A Convergence of Advanced Materials, Cells, and Microscale Technologies

“…The most critical consideration for in vitro models is the reproduction of a desired in vivo organ by selecting a suitable cell type from an appropriate cell source . While animals were the main source of cells for TE, they fail to mimic the human functionality and complexity .…”

Controlling Differentiation of Stem Cells for Developing Personalized Organ‐on‐Chip Platforms

“…One promising approach is to exploit the strength of biomimetic skin‐on‐a‐chip platforms for achieving HT assays to examine various aspects of drug development and disease modeling, as highlighted by our team elsewhere . Skin tissues have also been incorporated in several multiorgan platforms with the purpose of exploring the cross‐talk and metabolic activities of the skin tissue with other tissues in the body like the liver and kidney . While microfluidic devices have promoted the function of engineered skin tissue models, several challenges remain to be addressed.…”

“…In a search for an approach to represent intricate pathophysiology and human‐relevant conditions, 3D in vitro models were introduced. Tissue‐engineered models, 3D bioreactors, hydrogel‐based constructs, spheroids (organoids) and hanging drop (multi) organ cultures, and static or fluidically connected cocultures are examples of 3D culture systems. These models have been developed to recapitulate in vivo behavior of healthy and diseased conditions of different tissues, including cardiac muscles and cardiomyopathy, intestinal organoids, brain organoids, liver infections, mechanosensory circuits, and atrophic skeletal muscle .…”

“…Since OOCs are microfluidic devices that deal with minute amounts of culture medium, cells, and other reagents, they can also significantly reduce the cost of expensive reagents . Multiorgan models have also been proposed to investigate organ–organ interactions and to characterize the organ‐specific responses to drug candidates . Providing organ level and multiple tissues with the mimetic structural as well as functional complexity is crucial for obtaining valid results on drug efficacy.…”

“…Providing organ level and multiple tissues with the mimetic structural as well as functional complexity is crucial for obtaining valid results on drug efficacy. Examples of microengineered OOCs, successful in the biomimetic testing of drug candidates, are heart‐on‐a‐chip, cancer‐on‐a‐chip, multiorgan models, and neural network (brain)‐on‐a‐chip models …”