Researchers develop “organ on a chip” for better drug testing 

Funding of 2 million dollars has enabled the 3D printing of synthetic models that mimic part of the human brain and could replace the use of animals in the development of treatments. 

Improving quality of life through pharmaceuticals is a complex endeavor that requires extensive testing and government approval. Testing new drugs is complicated by ethical and biological concerns, especially when it comes to animal testing. As the biological make-up of animals and humans is different, there are increasing calls to replace animal testing. An international team of researchers, including Jeff Schultz from Virginia Tech, has developed a solution that does not require human or animal test subjects. Instead, the team is using new technologies to create highly customizable test environments in which drugs can be tested with cells.

The project is funded by a 1.8 million dollar grant from the National Institutes of Health (NIH). Researchers involved include Amrinder Nain, professor of mechanical engineering at Virginia Tech, Rafael Davalos, professor at Georgia Tech, Seemantini Nadkarni of Harvard Medical School, and Jeff Schultz, co-founder of Phase Inc, a company specializing in 3D-printed microfluidics.

A key obstacle in drug development is the blood-brain barrier, which allows beneficial substances into the brain and keeps harmful ones out. Replicating this complex barrier for testing has been difficult, which has often led to the failure of clinical trials.

“Therapeutics fail in clinical trials because they can’t cross the blood-brain barrier,” said Davalos. “The reality is that the devices that have been created in a lab don’t work and they allow too much to pass through. This gives false information that molecules can get through, and when you get into a clinical trial, the drugs fail because the human brain conditions haven’t been properly duplicated.”

The team is using Phase Inc.’s proprietary 3D printing method to create microfluidic devices at unprecedented resolution. These devices simulate the functioning of human organs and make it possible to test drugs under realistic conditions.

“We’re building something that more realistically mimics the geometry of the body compared to other microfluidics,” said Schultz. “Harnessing the design freedom of 3D printing allows us to create devices that have the same curvature, size of veins, and functionality of the human body. We can put in valves similar to the heart that are accustomed to pulsating mechanical stresses. This gives us the opportunity to see results that are closer to real life than if the cells were laying flat in a dish, and is done in other conventional microfluidic devices, but has yet to be applied to the blood brain barrier.”

In the first phase of the project, Schultz and Davalos developed a method for 3D printing polydimethylsiloxane (PDMS), a silicone polymer that can mimic the blood-brain barrier.

“The challenge we set out to solve was with the materials,” said Schultz. “There were no materials you could 3D-print for microfluidics that were widely accepted as safe for cells. PDMS was used for over two decades but wasn’t 3D printable. We set out to develop a technology to 3D-print that material, which the NIH funded us to do in phase one of the project.”

PDMS had been used for over two decades but was not 3D printable. By developing a technology to 3D print this material, the team was able to take the first step towards creating an artificial blood-brain barrier.

After the success of the first phase, the team expanded the project. Amrinder Nain contributed with his expertise in nanofiber membranes that function similarly to living tissues. These membranes became the key to the next development and enabled the team to obtain further NIH funding. Nain’s group developed an ultrathin and highly porous blood-brain barrier that is about 70 percent thinner than previous models.

“Organ-on-a-chip technologies are now projected to be standard lab protocols in the 21st century,” said Nain. “Our technological breakthroughs have enabled the thinnest BBB in the market. In future design iterations, we expect to meet the dimensions and architectures present in the human body to achieve physiological outputs in a lab setting. When realized, this will transform how we test drugs and study bioengineering and biophysics.”

These developments will provide future researchers with a reliable tool for faster and more accurate drug testing in physiologically relevant environments and reduce the need for animal testing.