A miniature replica of a heart chamber made from engineered parts and tissue from stem cells—and all contained on a chip not much bigger than a postage stamp—could help researchers study disease and test new treatments. Credit: Jackie Ricciardi for Boston University Photography
Scientists at Boston University may have just solved the largest hurdle of heart research: getting a close-up view of exactly how the organ functions.
Over the years, scientists have used different models in heart research, including cadaver hearts and lab-grown tissues, but none have been able to perfectly replicate the ticker. Now, an interdisciplinary team of engineers, biologists and geneticists solved this limitation by building a miniature replica of a heart chamber from nanoengineered parts and human heart tissue.
“We don’t think previous methods of studying heart tissue capture the way the muscle would respond in your body,” said Christopher Chen, director of Boston University’s Biological Design Center. “This gives us the first opportunity to build something that mechanically is more similar to what we think the heart is actually experiencing—it’s a big step forward.”
At just 3 square centimeters, the miniPUMP—officially known as the cardiac miniaturized precision-enabled unidirectional microfluidic pump—isn’t much bigger than a postage stamp. The researchers used a process called two-photon direct laser writing—a more precise version of 3D printing—to create the working components of the pump. There are no springs or external power sources—like the real thing, it just beats by itself, driven by live heart tissue grown from stem cells.
A large-scale replica of the scaffold that supports
the heart tissue. In the miniPUMP, the scaffold is
tiny—with many parts measured in microns. At such
a fine scale, ordinarily stiff materials become flexible.
Credit:Christos Michas, courtesy of Alice White’s lab
Built to act like a human heart ventricle, the miniPUMP features miniature acrylic valves and small tubes that mimic how blood—or water for the purposes of this study—is pumped and distributed throughout the human body.
Perhaps the most critical part of the miniPUMP is an acrylic scaffold that supports and moves with the heart tissue as it contracts.Comprised of a series of super-fine concentric spirals connected by horizontal rings, the scaffold gives structure to the heart cells, but does not exert any active force on them. This is especially important as it allows the researchers to ensure they are generating data replicate to the larger human version of the heart.
In the corner of the pump, surrounded by the scaffold, lies cardiomyocytes—the cells that make human heart tissue contract—made using induced pluripotent stem cells.
Christos Michas, the Boston University postdoctoral researcher who designed and led the development of the miniPUMP, said the cardiomyocytes give the pump enormous potential in helping pioneer personalized medicines.
“With this system, if I take cells from you, I can see how a drug would react in you because these are your [specific] cells,” said Michas. “This system replicates better some of the function of the heart, but at the same time, gives us the flexibility of having different humans that it replicates. It’s a more predictive model to see what would happen in humans—without actually getting into humans.”
If that turns out to be true, the miniPUMP could eventually speed up the drug development process, making it faster and cheaper. Instead of spending $2 billion and 20 years of R&D on a new drug only to see it fail in human clinical trials, scientists could use the miniPUMP at the outset to better predict success or failure.
“At the very beginning, when we’re still playing with cells, we can introduce these devices and have more accurate predictions of what will happen in clinical trials,” said Michas. “It will also mean that the drugs might have fewer side effects.”
The device also enables the study of disease progression in a way that hasn’t been possible before—and that’s not limited to hearts.
“We chose to work on heart tissue because of its particularly complicated mechanics, but we showed that, when you take nanotechnology and marry it with tissue engineering, there’s potential for replicating this for multiple organs,” anything from lungs to kidneys, explained Alice White, professor of mechanical engineering at Boston University.
In the immediate future, the researchers say they plan to refine the technology by testing ways to manufacture the device without compromising its reliability.