Researchers at The Ohio State University have developed a ventilator-on-a-chip model to measure lung functions.

The miniature organ-on-a-chip model allows researchers to directly compare different kinds of injury mechanical ventilation causes to the lung cells. The researchers have found that shear stress from the collapse and reopening of the air sacs is the most injurious damage.

Ohio State’s ventilator-on-a-chip model simulates lung injury during mechanical ventilation and repair and recovery in human-derived cells in real-time.

“The initial damage is purely physical, but the processes after that are biological in nature – and what we’re doing with this device is coupling the two,” co-lead author Samir Ghadiali said in a news release.

The researchers hope the device will help discover new therapies for ventilator-induced lung injuries.

“This is an important advance in the field that will hopefully allow for a better understanding of how lung injury develops in mechanically ventilated patients and identification of therapeutic targets so that we can give drugs to prevent that kind of injury or treat it when it happens,” said co-lead author Joshua Englert, associate professor of pulmonary, critical care and sleep medicine at Ohio State University Wexner Medical Center.

How the ventilator-on-a-chip is designed

Gold standard ventilators are designed to save the lives of patients who have severe respiratory problems related to disease or trauma. They were an essential medical product during the COVID-19 pandemic. However, the mechanical forces exerted on the lungs can also cause injuries. The researchers suggest that damage at the cellular level can make the barrier between tiny air sacs and capillaries carrying blood to become leaky, leading to fluid buildup that interferes with oxygen getting into the lungs.

“We knew for a long time that collapse and reopening is a pretty injurious force, but we never could measure it in real-time,” Ghadiali said. “Now that we know that collapse and reopening injury happens much quicker and takes a long time to recover, we plan to use the ventilator on a chip to figure out how to prevent this injury and/or enhance the repair.”

The ventilator-on-a-chip measures real-time changes to cells that affect the barrier’s integrity. The researchers designed it using growing human lung cells on a synthetic nanofiber membrane, mimicking the complex lung matrix. According to the researchers, the chip resembles an authentic ventilated lung microenvironment more closely than any similar lung chip systems.

The device measures the effects of three types of mechanical stress on the lung barrier, including lung cell stretch from overinflation, increased pressure on lung cells, and cyclical collapse and reopening of air sacs.

Research using the chip has shown that overinflation with a high volume of air and cyclic collapse and reopening of air sacs led to the barrier becoming leaky. Still, the cells recovered quickly from overinflation, more than from the repetitive opening and closing of air sacs.

“There really hasn’t been a lot of data that could allow for the comparison of those two injurious forces in the same system,” Englert said. “But now for the first time, we can use the same device with the same cells and induce both types of injury and see what happens. Our data suggests neither one of them is good, they’re both injurious, but that the collapse and reopening seems to be more severe and makes recovery harder.”

Next steps

Now, the researchers hope to model diseases like pneumonia and traumatic injuries that ICU patients experience in combination with mechanical action.

“We’re in the early stages of developing some of those models, diving a little bit deeper into the complexity of lung injury in ICU patients,” Englert said. “This model is a platform we can build upon.”

The research was published in the Lab on a Chip journal and was supported by the National Institutes of Health and the U.S. Department of Defense.