Researchers are working towards building a multi-channel 3D microfluidic cell culture system that compartmentalizes microenvironments in which 3D cellular aggregates are cultured to mimic multiple organs in the body. Most organ-on-a-chip models today only culture one cell type, so even though they may be valid models for studying whole organ functions, the systemic effect of a drug on the human body is not verified.
In particular, an integrated cell culture analog (μCCA) was developed and included lung cells, drug-metabolizing liver and fat cells. The cells were linked in a 2D fluidic network with culture medium circulating as a blood surrogate, thus efficiently providing a nutritional delivery transport system, while simultaneously removing wastes from the cells. "The development of the μCCA laid the foundation for a realistic in vitro pharmacokinetic model and provided an integrated biomimetic system for culturing multiple cell types with high fidelity to in vivo situations", claim C. Zhang et al. They have developed a microfluidic human-on-a-chip, culturing four different cell types to mimic four human organs: liver, lung, kidney and fat. They focused on developing a standard serum-free culture media that would be valuable to all cell types included in the device. Optimized standard media are generally targeted to one specific cell-type, whereas a human-on-a-chip will evidently require a common medium (CM). In fact, they claim to have identified a cell culture CM that, when used to perfuse all cell cultures in the microfluidic device, maintains the cells' functional levels. Heightening the sensitivity of the in vitro cultured cells ensures the validity of the device, or that any drug injected into the microchannels will stimulate an identical physiological and metabolic reaction from the sample cells as whole organs in humans.
A human-on-a-chip design that allows tuning microfluidic transport to multiple tissues using a single fluidic actuator was designed and evaluated for modelling prediabetic hyperglycaemia using liver and pancreatic tissues.
With more extensive development of these kinds of chips, pharmaceutical companies will potentially be able to measure direct effects of one organ's reaction on another. For instance, the delivery of biochemical substances would be screened to confirm that even though it may benefit one cell type, it does not compromise the functions of others. It is probably already possible to print these organs with 3D printers, but the cost is too high. Designing whole body biomimetic devices addresses a major reservation that pharmaceutical companies have towards organs-on-chips, namely the isolation of organs. As these devices become more and more accessible, the complexity of the design increases exponentially. Systems will soon have to simultaneously provide mechanical perturbation and fluid flow through a circulatory system. "Anything that requires dynamic control rather than just static control is a challenge", says Takayama from the University of Michigan. This challenge has been partially tackled by tissue engineering Linda Griffith group from MIT. A complex multi-organ-on-a-chip was developed to have 4, 7, or 10 organs interconnected through fluidic control. The system is able to maintain the function of these organs for weeks.
