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Organs-on-Chips: Mimicking the Heart on a Microchip

Heart failure is a chronic, progressive condition in which the heart muscle is unable to pump enough blood to meet the body’s needs for blood and oxygen. In other words, the heart cannot keep up with its workload. The causes for heart failure vary, ranging from prenatal heart defects and coronary artery disease to obesity and sleep apnea.

“One specific cause of progressive heart failure is cardiac amyloidosis,” says Ashutosh Agarwal, an assistant professor in the College of Engineering’s Department of Biomedical Engineering. “Cardiac amyloidosis is a disorder caused by deposits of an abnormal protein – called amyloid – in the heart tissue. These deposits make it hard for the heart to work properly.”

In the past, cardiac amyloidosis was thought to be an untreatable and rapidly fatal disease. “A clear understanding of the mechanisms that promote this disease is important to identify and develop effective treatments,” says Agarwal. While significant advances have been made in the past decade in terms of developing disease models in animals, such as transgenic mice, many of these models take years to complete and do not accurately mimic the human condition.

Agarwal is collaborating with Rajeev Prabhakar, an associate professor in the College of Arts and Sciences’ Department of Chemistry, to develop a more accurate in vitro model of the human heart that will enable understanding and therapy development for cardiac amyloidosis. The collaborative research project, one of seven awards funded by the College of Engineering and the College of Arts and Sciences, focuses on the topics related to the Frost Institute of Chemistry and Molecular Science (FICMS), the first of the Frost Institutes for Science and Engineering that will be housed in the new Phillip and Patricia Frost Science and Engineering Building.

The collaborative research effort will focus on using adapted computer microchip manufacturing methods to engineer microfluidic culture devices that mimic the microarchitecture and functions of the heart. These microdevices, called ‘organs-on-chips’, can be used to continuously monitor and quantitatively characterize the electrophysiological properties of heart’s cells, without adversely affecting them.

“Using organs-on-chips, it is now feasible to create the cellular microenvironments of healthy and diseased tissues and engineer biological systems with high precision,” explains Agarwal. “Specifically, cardiac tissues can be grown in physiologically realistic systems, which mimic both the architecture of the muscular systems surrounding the heart as well as the mechanical properties of the heart’s muscular tissue.”

By creating a heart-on-a-chip, Agarwal and Prabhakar will be able to accurately model cardiac amyloidosis, providing researchers worldwide the means to develop and optimize therapeutic strategies for individual patients of the disease. “Rapid disease progression, reduced therapeutic options, and poor survival rate make cardiac amyloidosis management difficult,” explains Agarwal. “These issues highlight the urgent need for an accurate in vitro disease model of the human heart.”

The research project it officially titled, “Cardiac Amyloidosis on a Chip.” To learn more about organs-on-chips, please click here.

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