A new ‘heart attack on a chip’ could serve as a test bed for developing personalized drugs

Researchers from the Alfred E. Mann Department of Biomedical Engineering at the University of Southern California have developed a “heart attack on a chip,” a device that could one day serve as a test bed for developing new heart drugs and even personalized drugs.

“Our device replicates some key features of a heart attack in a relatively simple and easy-to-use system,” said Megan McCain, associate professor of biomedical engineering and stem cell biology and regenerative medicine, who developed the device. with postdoctoral researcher Megan Rexius-Salle.

This allows us to better understand how the heart changes after a heart attack. From there, we and others can develop and test drugs that will be most effective in limiting the further breakdown of heart tissue that can occur after a heart attack.”

Alfred E. Mann, Department of Biomedical Engineering, University of Southern California

McCain, a “cardiac tissue engineer”, whose work previously included the co-development of a heart-on-a-chip, and Rexius-Hall detail their findings in a recently published article in the journal Scientists progress titled “Myocardial Infarction Border Zone on a Microchip Demonstrates Distinct Regulation of Cardiac Tissue Function by an Oxygen Gradient.”

America’s number one killer

Coronary heart disease is the leading cause of death in the United States. In 2018, 360,900 Americans succumbed to it, making heart disease responsible for 12.6% of all deaths in the United States, according to the AHA. Severe coronary artery disease can cause a heart attack, which accounts for much of this pain and suffering. Heart attacks occur when fat, cholesterol, and other substances in the coronary arteries dramatically reduce the flow of oxygen-rich blood to part of the heart. Between 2005 and 2014, an average of 805,000 Americans a year had heart attacks.

Even if a patient survives a heart attack, over time they may become increasingly tired, edgy and ill; some even die from heart failure. This is because heart cells do not regenerate like other muscle cells. Instead, immune cells appear at the site of injury, some of which can be harmful. Additionally, scars develop which weaken the heart and the amount of blood it can pump.

However, scientists do not fully understand this process, particularly how heart cells in healthy and injured parts of the heart communicate with each other and how and why they change after a heart attack.

McCain and Rexius-Hall think their on-chip heart attack can shed light on these mysteries.

“Basically, we want to have a model that can lead to a better understanding of heart attack injury,” Rexius-Hall said.

Heart attack on chip

Heart Attack on a Chip is literally built from the ground up. At the base is a 22 millimeter by 22 millimeter square microfluidic device slightly larger than a quarter – made from a rubbery polymer called PDMS – with two channels on opposite sides through which gases flow. Above is a very thin layer of the same rubber material, which is permeable to oxygen. A microlayer of protein is then patterned on top of the chip, “so that the heart cells line up and form the same architecture that we have in our hearts,” McCain said. Finally, rodent heart cells are grown on top of the protein.

To mimic a heart attack, gas with oxygen and gas without oxygen is released through each channel of the microfluidic device, “exposing our heart on a chip to an oxygen gradient, similar to what actually happens during of a heart attack,” McCain said.

Because the microfluidic device is small, clear and easy to see under a microscope, McCain added, it also allows researchers to observe in real time the functional changes that sometimes occur in the heart after a stroke, including an arrhythmia or an irregular heartbeat, and contractile dysfunction, or a decrease in the force of contraction of the heart. In the future, researchers may make the model more complex by adding immune cells or fibroblasts, the cells that generate the scar after a heart attack.

In contrast, researchers cannot observe heart tissue changes in real time with animal models. Additionally, traditional cell culture models uniformly expose heart cells to high, medium, or low oxygen levels, but not to a gradient. That means they can’t mimic what actually happens to damaged heart cells in the so-called border zone after a heart attack, Rexius-Hall said.

McCain added: “It is very exciting and rewarding to imagine our device having a positive impact on the lives of patients in the near future, especially for heart attacks, which are extremely common. »

Other co-authors of this article include Natalie Khalil, who holds a doctorate from USC Viterbi. biomedical engineering student; Sean Escopete and Sarah Parker of the Smidt Heart Institute at Cedars-Sinai Medical Center; and Xin Li, Jiayi Hu, Hongyan Yuan from the Department of Mechanics and Aerospace Engineering, Southern University of Science and Technology in China.

The National Heart, Lung, and Blood Institute and the American Heart Association (AHA) supported this research.