Current research in vitro liver cell culture models leans toward the goal of increasing predictability.

Manufacturing 2D micropatterned, and microfluidic devices with 3D printed components is driving advancements to help maintain stable culture conditions for accuracy. These devices can be critical parts of the models for early stage-drug and vaccine development in the pharmaceutical industry.

Dr. Sangeeta Bhatia’s research team at MIT has developed micropatterned co-cultures (MPCC) as a potential solution for stable in vitro hepatocyte modeling. They prepared primary human hepatocytes in 2D islands. The cell culture chamber was made of a PDMA etched mask and an extracellular coated well plate. Collagen islands were adsorbed on the PDMA surface, and the hepatocytes were micropatterned into the islands. The surrounding area was covered in fibroblast cells for support. The device was used with repeatable results during the life cycle evaluations of hepatocytes between 4 to 6 weeks during exposure studies to the liver pathogens, hepatitis B, hepatitis C, as well as the major malaria parasites, Plasmodium falciparum, and Plasmodium vivax.

Dr. Michael Schuler’s research team at Cornell University found that hepatocytes can have increased, responsive metabolic activity while in a microfluidic device with bi-directional fluid flow compared to an immobile device. The device is considered low cost, as it is pumpless and the flow is gravity driven. The cell culture chambers were made of silicone gaskets that hold the 3D printed parts with the fluidic channels. The liver tissue scaffold sandwiches between the 3D printed parts. Various type of liver cells are held in the scaffold, such as hepatocytes and non-nonparenchymal cells, (fibroblasts, stellate cells, and Kupffer cells). The cells received P450 inducers and bacterial lipoprotein from the top and bottom in the 14-day culture test as the proof of concept to evaluate hepatoxicity.