Modelling human liver microphysiology on a chip through a finite element based design approach.

Area of Science:

• Biotechnology
• Bioengineering
• In vitro modeling

Background:

• Organ-on-a-chip (OoaC) technology offers advanced in vitro models for biological research and healthcare.
• Finite element modeling (FEM) is crucial for simulating OoaC microenvironments and optimizing device design.
• Accurate replication of in vivo organ microenvironments, such as oxygen gradients in the liver, is essential for reliable OoaC models.

Purpose of the Study:

• To refine a steady-state gradient generator for a more relevant human liver-on-a-chip model.
• To utilize FEM to predict design parameters that best replicate in vivo liver oxygen gradients.
• To develop an optimized OoaC device for studying liver zonation and improving liver tissue culture.

Main Methods:

• Organ-on-a-chip (OoaC) device design and fabrication.
• Finite element method (FEM) for simulating fluid dynamics and oxygen gradients.
• In vitro validation using literature-based examples and comparison with in vivo data.

Main Results:

• A novel liver gradient-on-a-chip was developed, achieving oxygen concentration gradients from 3% to 12%.
• The model accurately correlates with in vivo oxygen zonation in human liver acini (perivenous: 3%-5%, periportal: 10%-12%).
• Simulated shear stress averaged 0.037 Pa, falling within the optimal range for liver tissue culture (0.01–0.05 Pa).

Conclusions:

• FEM is an effective tool for optimizing OoaC device design and achieving specific physiological conditions.
• The developed liver gradient-on-a-chip provides a more relevant in vitro model for liver research.
• This technology has the potential to advance drug screening and disease modeling using human organoids.