Scientists have made significant progress in understanding the various types of injuries that mechanical ventilation inflicts on lung cells. A recent study using an innovative “ventilator-on-a-chip” model revealed that the shear stress linked to the collapsing and reopening of air sacs is the most damaging form of injury.
For the first time, scientists can directly analyze the different kinds of injuries that mechanical ventilation inflicts on lung cells.
In this new study, which utilized a ventilator-on-a-chip model designed at The Ohio State University, the researchers found that the shear stress resulting from the expansion and contraction of the air sacs is the most harmful type of damage.
This miniature “organ-on-a-chip” model not only simulates lung injuries caused by mechanical ventilation but also replicates the repair and recovery processes in human-derived cells in real-time, according to co-lead author Samir Ghadiali, PhD, who is a professor and chair of biomedical engineering at Ohio State.
“The primary damage is purely physical, but the subsequent processes are biological in nature. Our device connects these two aspects,” Ghadiali explained.
The research team aims for the device to assist in finding treatments for ventilator-induced lung injuries.
“This represents a crucial advancement in the field, which will hopefully lead to a better understanding of how lung injuries arise in patients on mechanical ventilation and help identify potential therapeutic targets for preventing or treating such injuries,” stated Joshua Englert, MD, co-lead author and associate professor of pulmonary, critical care, and sleep medicine at The Ohio State University Wexner Medical Center.
The findings of this research were recently published in the journal Lab on a Chip.
While ventilators are essential for saving the lives of patients facing severe respiratory issues due to illness or injury, it has long been known that the mechanical forces they exert can also inflict damage. At the cellular level, this injury can cause the barrier between tiny air sacs and blood-carrying capillaries to become leaky, which leads to fluid accumulation and hinders oxygen absorption by the lungs.
The chip’s ability to measure real-time changes in cells that affect barrier integrity is particularly valuable. This is achieved through a novel method that involves growing human lung cells on a synthetic nanofiber membrane designed to mimic the intricate structure of lung tissue. Researchers assert that this model replicates the ventilated lung environment more accurately than any existing lung chip systems.
The device gauges the effects of three types of mechanical stress on barrier integrity: lung cell stretching from overinflation, increased pressure on lung cells, and the cyclic collapse and reopening of air sacs.
Experiments indicated that both high-volume overinflation and the cyclic collapse and reopening of air sacs resulted in barrier leakage, but cells were able to recover from overinflation more swiftly than they could from the repetitive collapse and reopening process.
Englert noted that the latter may pose more significant issues since it causes lung fluid movement, thereby exposing cells to elevated shear stress levels.
“There has previously been limited data comparing these two damaging forces within the same system,” Englert said. “Now, for the first time, we can use the same device and the same cells to induce both types of injuries and analyze the outcomes. Our findings suggest that although both injuries are detrimental, the collapse and reopening of the air sacs appears to be more severe and complicates recovery.”
This discovery showcases the sophistication of the model, according to Ghadiali.
“We have known that collapse and reopening is a significant injury factor for some time, yet we were unable to gauge it in real-time,” he commented. “Now that we understand that this type of injury occurs more rapidly and takes longer to heal, we intend to use the ventilator-on-a-chip to explore methods for preventing or improving the repair of such injuries.”
Future research will involve modeling diseases like pneumonia and traumatic injuries that ICU patients face alongside mechanical ventilation.
“We are at the early stages of creating these models, delving deeper into the complexities of lung injuries in ICU patients,” Englert remarked. “This model serves as a foundational platform for our research.”
Ghadiali and Englert, who are also part of Ohio State’s Davis Heart and Lung Research Institute, expressed gratitude to first author Basia Gabela-Zuniga, who recently completed her PhD in biomedical engineering, for her perseverance in completing the project. They also acknowledged contributions from Heather Powell and Natalia Higuita-Castro from the College of Engineering, as well as co-authors Vasudha Shukla and Christopher Bobba of Ohio State.
This research was funded by the National Institutes of Health and the U.S. Department of Defense.
