Research by University at Buffalo biomedical engineers Ruogang Zhao and Yun Wu may help discover new drugs to treat pulmonary fibrosis, a severe lung disease that can be life-threatening.
Pulmonary fibrosis has many causes, including smoking, ageing, environmental factors and viral infections, such as those associated with COVID-19. There is currently no cure, and the majority of drugs designed to treat it have failed clinical trials.
The image on the left shows microtissue arrays in a 12-well plate. Each plate has eight rows and eight columns for a total of 64 microtissues, and every bright fluorescent spot represents one microtissue. A scanning electron microscopy image of microtissue supported by a group of eight micropillars is shown on the right. Micropillars serve as force sensors to report the mechanical properties of the microtissue. Scale bar = 200 micrometer. Image credit: Ruogang Zhao, University at Buffalo.
“The main obstacles to the development of anti-pulmonary fibrosis drugs are the slow progression of the disease and the high cost and large sample size needed for animal studies and clinical trials,” says Zhao, PhD, associate professor in the Department of Biomedical Engineering, a joint program of the School of Engineering and Applied Sciences and the Jacobs School of Medicine and Biomedical Sciences at UB.
Clinical trials are typically expensive and existing preclinical models are limited in their ability to study the role of inflammation, which is one of the major contributors to the disease.
In a new research project funded by a $920,000, two-year grant from the National Heart, Lung and Blood Institute, which is part of the National Institutes of Health, Zhao and co-investigator Yun Wu, PhD, also an associate professor in the Department of Biomedical Engineering, will develop a new preclinical model to study inflammation-induced fibrosis to better understand the causes of fibrosis disease and evaluate the therapeutic efficacy of potential drug candidates.
“We hope that our work will expedite the translation of drug candidates from the laboratory to clinics, and that this technological advancement will positively impact current practice to combat fibrotic diseases,” says Zhao. “Furthermore, since pulmonary fibrosis is one of the major sequela of COVID-19, it is possible that this research can help discover treatments for people infected with the disease and contribute to the battle against the pandemic.”
Zhao and his team are using microfabrication to create 3D patterns that are about the same diameter as a single human hair, called microtissues. An array of these microtissues allows high-throughput testing of the drug candidates. The microfabricated tissue array system can then be used to study the mechanism of inflammation-induced fibrosis and detect changes in the tissue stiffness, which is closely related to fibrosis progression or reversal under drug treatment.
“Ruogang’s research is an excellent example of how biomedical engineering directly impacts the lives of many people. He and Yun are developing new knowledge and tools that can improve drug development and ultimately lower costs. This is really exciting work,” says Albert Titus, professor and chair of the Department of Biomedical Engineering.
Zhao’s research interests include developing advanced biofabrication technologies, such as organ-on-chip models and 3D bioprinting for disease modeling, drug screening and injury repair. By combining these technologies with biomechanics, he has developed a unique research program to address the unmet need to model the physiology and pathology of mechanosensitive diseases such as tissue fibrosis.