3D ‘lung-on-a-chip’ replicates human lungs for medical study

Developed by a team from Brigham and Women’s Hospital, the device replicates distal lung and alveolar structures: the tiny air sacs in which the lungs and blood exchange oxygen and carbon dioxide as the body inhales and exhales.

Notably, this technology enables scientists to investigate how various Covid-19 therapies, such as remdesivir, impact the replication of the virus.

Bioengineer Professor Y. Shrike Zhang said: “This is a first-of-its-kind in vitro model of the human lower lung that can be used to test many of the biological mechanisms and therapeutic agents, including anti-viral drugs for Covid-19 research.”

Understanding and developing treatments for Covid-19 requires human clinical trials which are typically both time and resource intensive. The researchers hope the new device will enable drugs to be evaluated much faster and help select the drug candidates most likely to succeed in clinical trials.

The technology has been designed to mirror the biological characteristics of the human distal lung. Previous models have been based on flat surfaces and oftentimes made with plastic materials, which do not incorporate the curvature of the alveoli and are much stiffer than the human tissue. The lung-on-a-chip has been created with materials more representative of human alveolar tissue and stimulated cell growth within these 3D spaces.

In testing the model’s effectiveness, the researchers found that the 3D alveolar lung effectively grew cells over multiple days and that these cells adequately populated airway surfaces. Through genome sequencing, scientists observed that the alveolar lung model more closely resembled the human distal lung than existing 2D models. Additionally, the lung-on-a-chip model successfully stimulated breaths of air at the normal frequency for humans.

Beyond Covid-19, it is hoped the device could be used to study a broad range of pulmonary conditions, including various lung cancers. To replicate smoking’s impact on the lungs, scientists allowed smoke to seep into the model’s air chambers then simulated a breathing event, moving smoke deeper into the lungs. From there, they assessed damage caused by the smoke.

Currently, the alveolar lung-on-a-chip only incorporates two out of the 42 cell types in the human lung, but the researchers hope to expand upon this significantly to make it more clinically representative of human lungs.

“In terms of Covid-19, we’ve had very minimal timelines for developing therapies. In the future, if we have these models ready in hand, we can easily use them to study and test therapeutics in urgent situations where clinical trials are limited,” said Zhang.