By Madeleine Stone @themadstone

Nature is often said to be the greatest innovator. University of Pennsylvania engineer Dan Huh, a pioneer in the development of “organs-on-chips,” tiny, three-dimensional models of living human organs, uses nature’s creativity as a source of inspiration.

“I try to learn from the design principles invented by nature,” Huh said. “Organ-on-a-chip systems simulate our own physiology so that we can better understand it.”

Huh, the Wilf Family Term Assistant Professor in the School of Engineering and Applied Science’s Department of Bioengineering, is now a recipient of an NIH New Innovator Award. The highly competitive award grants Huh $1.5 million during the next five years to develop microfabricated systems that mimic diseased human lungs. This technology could help researchers to better understand the progression of chronic lung diseases, including asthma, and develop effective therapeutics against them.

Before beginning his position at Penn in August 2013, Huh was a postdoctoral research fellow at Harvard University’s Wyss Institute, where he worked with Donald Ingber to develop the first organs-on-chips. Composed of living human tissue on a flexible polymeric scaffold in a three-dimensional microfluidic device, these eraser-sized structures represent accurate models of human organs. Applications range from basic physiological research to drug testing and environmental monitoring.

At Penn, Huh is continuing to develop microfabricated systems for biomedical applications. A key focus of Huh’s research group is designing better models for human disease.

“Researchers traditionally use cell cultures or animal models to study disease,” Huh said. “But often, these models fail to accurately simulate key biological processes that mediate disease progression and exacerbation in humans. Using our microengineered model systems that mimic the most salient features of living human organs, we may be able to better understand the underlying mechanisms of various diseases and develop more effective drugs.”

With the support of the NIH award, Huh’s research team will begin to develop three-dimensional models of small-sized airways, air passages measuring less than 2 millimeters in diameter, in the human lung.

“There is convincing evidence that small airways deep in the lung play an important role in asthma,” Huh said. “But we lack fundamental understanding of how these airways contribute to the development and progression of the disease.”

During an asthma attack, lung cells experience abnormal mechanical forces produced by airway constriction and excess mucus. Huh’s proposed lung-disease-on-a-chip will allow him to reproduce the pathological biomechanical forces involved in asthma and study how these forces affect key disease processes such as airway inflammation and tissue remodeling.

NIH New Innovator Awards support young investigators with creative and potentially high-impact proposals. Huh’s organ-on-a-chip technology promises to help solve a range of challenges facing medical researchers, accelerating the translation of research into improved health care.

“Our work is driven by a need for new enabling tools in biology and medicine. Design of research in my group often begins with understanding the technical challenges faced by biologists and clinicians. This approach greatly facilitates our efforts to develop innovative bioengineering technologies with the potential to make a real impact,” Huh said.