A research team led by Wyss Institute core faculty member Kit Parker has discovered the mechanism that underlies the types of traumatic brain injuries (TBI) that soldiers in Iraq and Afghanistan are suffering as a result of roadside explosions. His recent work, which essentially creates a living concussion-on-a-chip, represents the latest milestone in the ongoing development of novel organ-on-chip technology being undertaken at the Institute.
The technology combines microfabrication techniques from the computer industry, with cutting-edge tissue engineering, and living human cells to recreate the complex functions of a human organ–in this case the brain.
Using a concussion-on-a-chip to model the physical and biochemical effects of TBI on the brain and blood vessels, Parker’s team was able to identify the cellular mechanism that translates mechanical forces into subtle, yet disastrous, physiological changes within the brain’s neurons and vasculature.
TBI is the most common injury facing soldiers in Iraq and Afghanistan. The jarring force of a roadside blast causes the delicate tissue of the brain to slam against the skull. The result, if the patient survives, can be a temporary concussion, a more dangerous hemorrhage, or long-term TBI, which can even lead to the early onset of Parkinson’s or Alzheimer’s diseases.
Parker’s team’s findings, which currently appear in both the Proceedings of the National Academy of Sciences and in PLoS One, offer urgently needed direction for research in therapeutic treatments by identifying potential drug targets. Their studies show that integrins, receptor proteins embedded in the cell membrane, provide the crucial link between external forces and internal physiological changes.
Parker oversees the Disease Biophysics Group, which is co-located at the Wyss and at Harvard’s School of Engineering and Applied Sciences. His dedication to TBI research was prompted by his own military service in Afghanistan where he was a first-hand witness to many of these injuries.
“So many young men and women are returning from military service with brain injuries, and we just don’t know how to help them,” says Parker. “This work is a solid first step toward creating an accurate model that could be used to screen for drugs to treat blast-injured soldiers before long-term damage sets in.”
Parker, along with Wyss Institute Founding Director Donald Ingber, is also working on a heart-lung micromachine with a $3 million grant from the National Institute of Health and the U.S. Food and Drug Administration. The proposed device will replicate the complex functions and mechanical microenvironment of a breathing lung and beating heart to assess the effects of new drugs on the integrated lung and heart function.
The initial embodiment of the organ-on-chip technology is a breathing human lung-on-a-chip, which mimics both the structure and the behavior of a breathing human lung to provide accurate and immediate measures of the safety and efficacy of new drug compounds.