Organ-on-a-chip: New approaches to the investigation of toxic chemicals

Researchers at the Wake Forest Institute for Regenerative Medicine are using 3D printing to better understand the effects of toxic chemicals on human lung tissue. Using organ-on-a-chip (OOAC) technology, artificial, living lung tissue is created on a microchip and then exposed to chemical vapors in a controlled manner. This approach is intended to provide more precise findings than previous test procedures, which are often based on animal testing or indirect methods.

The process is based on 3D bioprinting technology, in which living cells are integrated into a microstructured environment.

“The Organ-on-a-Chip studies that we are conducting with our partners at the Wake Forest Institute are incredibly important,” said CTC Project Manager Theresa Pennington. “With our OOAC program, we are 3D printing lung organ tissue equivalent (OTE) onto a microchip and then exposing that OTE to the toxic vapors. The reason for this approach is that the OTE more accurately represents how real lung tissue inside the human body reacts to the gaseous chemical agents than anything else we can use.”

“With WFIRM’s innovative Organ-on-a-Chip technologies, we can accurately replicate human responses to toxic chemical exposure,” said WFIRM Director Dr. Anthony Atala. “This groundbreaking research is a vital step toward enhancing safety measures and developing life-saving treatments, ultimately advancing our ability to understand and mitigate the impact of hazardous chemical agents on human health.”

A key advantage of this method is the high reproducibility of the tests. As the 3D printing process is computer-controlled, sources of error that can occur with manual cell cultures are minimized. In addition, the process allows a reduction in animal testing and offers more precise transferability to the human organism.

Wake Forest’s 3D printer for OTE represents a major leap forward over standard testing. “With Organ-on-a-Chip, we are able to design a lung tissue system using robotic technology,” said S&T CSAC Senior Research Scientist Rabih Jabbour. “We are able to 3D bio-print a lung model that mimics the microenvironment of a real human model. And it is living human tissue. So, in this case, we are directing a robot to do it, so we eliminate the possibility of human operator error. A robot always wins in terms of precision.”

“The entire microchip is only 1×2 inches or even smaller,” said Dr. Sean Murphy, WFIRM project co-lead “Within a permeable membrane lies the new OTE, and just like a real lung, it has tiny tubes inside it where air travels. These tubules are around 60 microns across, or about the thickness of a human hair. Air that contains the toxic chemical vapors is then pumped through those tubes to simulate as if someone was inhaling the fumes. That’s when the toxin interacts with the cells inside the tubes.”

In the long term, the method will be further developed and extended to other pollutants. Jabbour added, “We hope that this research in human response to exposure will assist in the future design and creation of effective medical countermeasures to mitigate or even possibly reverse the effects of these and other toxins so we can save lives.”

There are plenty of other dangerous chemical toxins in the threat space that the team also has on their collective radar. Moving forward, they hope to tackle ones like hydrogen sulfide and phosphine that do not have very accurate toxicity values. “Although this particular effort is wrapping up in December,” said Pennington, “we are hoping to identify additional funding so this incredibly important work can continue.”