Strategies for using mathematical modeling approaches to design and interpret multi-organ microphysiological systems...

Area of Science:

• Biotechnology and Biomedical Engineering
• Organ-on-a-chip technology
• Microphysiological systems (MPSs)

Background:

• Organ-on-a-chip technology now mimics human organs and diseases at the microscale.
• The next frontier is integrating organ modules into multiorgan microphysiological systems (MPSs), including body-on-a-chip models.
• These models aim to replicate complex inter-organ interactions and human physiology.

Purpose of the Study:

• To review mathematical methodologies for designing and interpreting multiorgan MPSs.
• To identify key considerations for accurately reflecting human physiology and disease in MPSs.
• To improve in vitro to in vivo translation for drug and chemical response studies.

Main Methods:

• Review of current mathematical modeling approaches, including scaling methods and pharmacokinetic models.
• Analysis of factors critical for multiorgan MPS design: organ size, flow rates, cell numbers, and ratios.
• Discussion of robust mathematical techniques for extrapolating MPS data to in vivo scenarios.

Main Results:

• Various mathematical models exist, each suited for specific objectives in multiorgan MPS research.
• Accurate recapitulation of human physiology and disease progression necessitates careful quantitative consideration of design parameters.
• Mathematical modeling is essential for both the design and interpretation of multiorgan MPS experiments.

Conclusions:

• Mathematical modeling is crucial for advancing body-on-a-chip technology and multiorgan MPS development.
• Addressing design factors and employing robust modeling will enhance physiological relevance and in vitro-in vivo translation.
• This work provides a framework for optimizing multiorgan MPS for better disease modeling and drug efficacy prediction.