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.
Highlights
Metabolism and toxicity analysis is one of the essential steps for drug design [1,2]
We have provided an overview of the principles of modeling predictive multi-organ models and highlighted the application of microfluidics and tissue engineering to develop experimental multi-organ platforms for drug testing and disease modeling
The platforms developed to date have been used to interconnect two or three organs together and have fairly tested a few drugs to evaluate how multi-organ systems can play significant roles in metabolisms of drugs
Summary
Metabolism and toxicity analysis is one of the essential steps for drug design [1,2]. In vitro models are traditionally based on static cell cultures in plates and provide a simple interface for testing the metabolism and toxicity of candidate drugs [7,8,9] These models lack the ability to mimic the in vivo cell-cell and cell-matrix interactions within the tissue microenvironment. Microtechnology has significantly contributed to the development of biomimetic in vitro models for predicting the drug efficacy with higher reliability than traditional models and organoid systems [13,14,15]. This technology has been utilized to develop integrated multi-organ platforms as an essential testing requirement during the advanced drug discovery steps. We discuss the challenges of developing biomimetic body-on-chip (BOC) models such as the scaling, cell types, selecting the suitable medium for all cell types, and optimizing the physiological parameters
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