Pulmonary thrombosis-on-a-chip offers glimpse into the inner workings of the lungs

IMG_0937_web.jpgCurrently, there is very little known about the biology of blood clotting within the lungs and how medications can be used to treat them. A blood clot that forms within the lungs is a death sentence for numerous patients every year. Anticoagulant drugs are given to patients to treat clots, but it is often not clear to the clinician what class of drug and what dosage is optimum for the patient without introducing undesirable toxic side effects. Dr. Abhishek Jain, assistant professor in the Department of Biomedical Engineering at Texas A&M University, is working to shed light into this issue by developing a new technology called pulmonary thrombosis-on-a-chip.

Jain, in conjunction with collaborators at the Wyss institute at Harvard University, Beth Israel & Deaconess Medical Center at Harvard Medical School, Emulate Inc., and Janssen Pharmaceutical Research and Development, has successfully created the first model of human pulmonary thrombosis in vitro. Their work has been published in Clinical Pharmacology & Therapeutics, a high-impact journal in the field.

“Scientists have methods that are currently in place, but they are either poor models or it simply becomes impossible to visualize what is actually happening within the lung,” Jain said. “To address this problem and to provide a new alternative to the current method for learning new biology, the pulmonary thrombosis-on-a-chip was developed.”

The research being conducted permits physiologically-relevant cellular and molecular analysis of vascular inflammation and thrombosis in human lungs, and offers a new method of assessment of medication before giving it to the patient, as well as discovering potential toxicities.

A salient feature of the pulmonary thrombosis-on-a-chip is that it allows whole blood added to the device to study the blood-tissue interactions at an organ-level inside lung alveolus. A future goal of the project is to include the motion of lung expansion and relaxation due to breathing, as well as incorporation of patient-specific cells using the human-induced pluripotent cells. This would in turn allow for reconstitution of more complex lung physiology and lead to personalized assessment of drug candidates.

As with any project of this magnitude, it comes with its list of challenges. Mass production of the devices in a way that the technology can easily be implemented within labs and other clinical settings is an issue. The good news is that advancements of 3-D printing with biocompatible materials could provide a viable solution. Jain is already tackling this challenge head on and working with materials scientists and clinicians at Texas A&M and the Texas Medical Center in Houston to develop “plug and play” organs-on-chips.

Jain joined the biomedical faculty at Texas A&M in the fall of 2016 and directs the Bioinspired Translational Microsystems Lab. His lab specializes in making microengineered models of cardiovascular and hematologic diseases for basic discovery, advancing the drug discovery process and enabling smart analytical technologies for precision and personalized healthcare.