Long-term maintenance of a microfluidic 3D human liver sinusoid

Area of Science:

• Biomedical Engineering
• Toxicology
• Organ-on-a-chip technology

Background:

• The National Institutes of Health (NIH) and Defense Advanced Research Projects Agency (DARPA) aim to replace animal drug testing with in vitro models.
• Developing long-term, human organotypic liver models is crucial for predicting drug toxicity accurately.

Purpose of the Study:

• To demonstrate the successful recapitulation of a liver sinusoid-on-a-chip using only human cells for 28 days.
• To establish a functional organotypic in vitro liver model that mimics the liver sinusoid microarchitecture.

Main Methods:

• Development of a microfluidic chip with two chambers separated by a porous membrane.
• Step-by-step construction of a 3D microtissue on-a-chip.
• Culture of human cells within the microfluidic device under flow conditions for 28 days.

Main Results:

• Successful maintenance of an organotypic liver-on-a-chip model for 28 days.
• The model recapitulated the liver sinusoid microarchitecture.
• Enhanced albumin synthesis and urea excretion were observed under flow conditions compared to static cultures.

Conclusions:

• A human liver-on-a-chip model can be successfully maintained for 28 days, replicating liver sinusoid microarchitecture.
• The model demonstrates improved liver functions (synthesis and detoxification) under flow.
• This human liver-on-a-chip holds potential for future drug toxicity studies.