Researchers have developed a novel fibrotic microtissue system to screen new drugs to treat pulmonary fibrosis, a type of lung disease where alveoli do not function correctly due to scarring and damage. Mimicking how pulmonary fibrosis damages and scars lung tissue over time has been challenging, making it difficult to develop treatments for the disease. The paper describing the new screening tool was published in Nature Communications.
This new tool is made up of a thin layer of lab-grown lung tissue fixed upon a chip array, similar to recently developed organ-on-a-chip technology.
"Obviously it's not an entire lung, but the technology can mimic the damaging effects of lung fibrosis. Ultimately, it could change how we test new drugs, making the process quicker and less expensive," says lead author Ruogang Zhao, PhD, assistant professor in the Department of Biomedical Engineering at the University at Buffalo.
The research team built small attachments made up a silicon-based organic polymer and printed them to the chip using microlithography. The tissue, placed on top of the attachments, was engineered to function like alveoli—the small air sacs in the lungs that take up oxygen. A protein was added that induced fibrosis causing the tissue to contract and stiffen which mimics the scarring that individuals with the actual disease experience. By measuring the bend in the silicon-based attachments the researchers were able to calculate tissue contraction force to measure the effectiveness of drug candidates.
The screening tool’s effectiveness was tested with the two approved drugs on the market to treat pulmonary fibrosis. The researchers measured a positive impact with both drugs which suggests the new lung-on-a-chip tool could be used to screen new drug candidates. The two existing drugs only treat one type of the disease but there are over 200 types of lung fibrosis and most do not have an approved treatment.
Image: Collagen from healthy engineered lung tissue. Image courtesy of Ruogang Zhao.