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

Area of Science:

• Biomedical Engineering
• Drug Discovery
• Translational Medicine

Background:

• Traditional preclinical drug screening models (cell culture, animal models) exhibit low predictive power for human response, leading to high clinical trial attrition rates.
• In vitro biomimetic models using human cells and physiologically relevant organ-organ interactions are emerging as
• human surrogates
• for improved drug effect prediction.

Purpose of the Study:

• To comprehensively review the development of tissue-engineered, human cell-based microscale multiorgan models, also known as multiorgan microphysiological systems (MPS), for drug testing.
• To discuss the evolution from traditional to macro- and microscale multiorgan systems and the rationale behind current global efforts in MPS development.

Main Methods:

• Review of scientific literature on tissue-engineered multiorgan systems.
• Analysis of advances in integrating cell culture and on-chip analytical technologies.
• Discussion of proof-of-concept applications and challenges in MPS development.

Main Results:

• Multiorgan microphysiological systems integrate advanced cell culture and on-chip technologies for in vitro drug testing.
• Various MPS configurations demonstrate potential for predicting human drug responses more accurately than traditional models.
• Key challenges include ensuring reproducibility and enhancing physiological relevance across different systems.

Conclusions:

• Multiorgan microphysiological systems represent a significant advancement in preclinical drug testing, offering enhanced predictive power.
• Ongoing research focuses on overcoming challenges in reproducibility and physiological relevance to further optimize these human surrogate models.
• Future trends point towards increasingly sophisticated and integrated multiorgan MPS for drug discovery and development.