This article uses a macroporous polymer scaffold to culture multiple liver cell types simultaneously under flow conditions. It compares scaffolds cultured under flow or static conditions and finds that flow results in elevations of both albumin and urea excretion; however, flow appears to have no significant effect on cytochrome p450 activity. The paper shows convincing evidence that the metabolic activity of the cells is increased (via albumin and urea measurements) in flow conditions and attributes this to increased opportunities for gas and metabolite exchange. The cell culture device is independent of pumps and tubing using gravity to produce the flow, making it simpler and less expensive, as well as offering potential as an organ-on-chip device. This device has thus potential for high throughput analysis due to its cheap price and simplicity. There are however a number of issues in the paper that would deserve further clarification and we would appreciate feedback from the authors. Firstly, all estimates of sheer stress and flow rates are mathematical simulations with no experimental data. Importantly, they also do not appear to take into account the effect that the presence of the scaffold within the device will have on the flow of media.
The second issue is that the authors do not mention how they count cell number. This is particularly important since all reported measurements are normalised per cell. If they simply use the seeding concentration as the number of cells, that could be a significant cause of error as it would assume not only that all cells bind to the scaffold but also that there is no change in cell number during the cell culture. Other minor issues with this work include limited evidence for the presence of the different cell types, figure 2C is very confusing as to which orientation the scaffold is in and they claim that the culture is ‘tissue like’ without any real supporting evidence.
In summary, the device offers a number of benefits due to its ability to culture primary hepatocytes for a prolonged period as well as showing evidence of improved metabolism compared with static systems but some important information is missing and additional work would be needed to fully support some of the conclusions.