Multiorgan Microphysiological Systems for Drug Development: Strategies, Advances, and Challenges

Abstract

Traditional cell culture and animal models utilized for preclinical drug screening have led to high attrition rates of drug candidates in clinical trials due to their low predictive power for human response. Alternative models using human cells to build in vitro biomimetics of the human body with physiologically relevant organ–organ interactions hold great potential to act as "human surrogates" and provide more accurate prediction of drug effects in humans. This review is a comprehensive investigation into the development of tissue-engineered human cell-based microscale multiorgan models, or multiorgan microphysiological systems for drug testing. The evolution from traditional models to macro- and microscale multiorgan systems is discussed in regards to the rationale for recent global efforts in multiorgan microphysiological systems. Current advances in integrating cell culture and on-chip analytical technologies, as well as proof-of-concept applications for these multiorgan microsystems are discussed. Major challenges for the field, such as reproducibility and physiological relevance, are discussed with comparisons of the strengths and weaknesses of various systems to solve these challenges. Conclusions focus on the current development stage of multiorgan microphysiological systems and new trends in the field.

Multiorgan microphysiological systems are in vitro microscale cell culture analog of the human body (body-on-a-chip). Tissue engineered single organ models are interconnected to reproduce complex multiorgan interactions. Such biomimetics of the human body can potentially serve as "human surrogates" to simulate human responses to drugs, providing pharmacokinetic and pharmacodynamic information.

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