New miniature heart

Now, an interdisciplinary team of engineers, biologists and geneticists has developed a new way to study the heart: They combined nanoengineered components and human heart tissue to create a miniature replica of the heart chamber

The team, led by Boston University, developed the tiny device, nicknamed the "mini-pump," which is officially known as a "precise unidirectional microfluidic pump" for the miniaturization of the heart

"We can study disease development in a way that was not possible before," said Alice White, a professor in Boston University's School of Engineering and chair of the Department of Mechanical Engineering

According to the researchers, the device could eventually speed up the drug development process, making it faster and cheaper

The project is part of CELL-MET, a multi-agency National Science Foundation Research Center for Cellular Metamaterials Engineering led by BU

"Heart disease is the number one cause of death in the United States, affecting us all," White said.

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"When the heart pumps blood through our body, it experiences complex forces," said Christopher Chen, the William F.

The tiny pump is only 3 cm², not much bigger than a postage stamp

"They were generated using induced pluripotent stem cells," said postdoctoral researcher Christos Michas, who designed and led the development of the micropumps as part of his doctoral thesis

To make cardiomyocytes, the researchers took a cell from an adult -- it could be a skin cell, a blood cell, or any other cell -- and recoded it into an embryonic stem-like cell, which was then turned into a heart cell

"With this system, if I take cells from you, I can see how the drug reacts in your body because these are your cells," Michas said

According to Michas, this could allow scientists to assess the chances of success of a new heart drug long before it enters clinical trials

"In the beginning, when we were still studying cells, we could introduce these devices and have a more accurate prediction of what would happen in a clinical trial," Michas said

thinner than human hair

One of the key components of the micropump is an acrylic stent that supports and moves with the heart tissue as it contracts

"We didn't think previous approaches to studying heart tissue captured the way human muscles respond," said Chen, who is also director of the Center for Biodesign at Boston University and an associate professor at Harvard's Wyss Institute for Biologically Inspired Engineering

To print each tiny part, the team used a process called two-photon direct laser writing -- a more precise form of 3D printing
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When light hits a liquid resin, the area it touches becomes a solid; because the light can be precisely aimed -- focused on a tiny spot -- many of the components in the micropump are micron-scale, smaller than a dust particle
.

Making this pump so small, rather than life-size or larger, was a deliberate decision that was critical to its function
.

"The structural elements are so fine-tuned that something that's normally hard becomes flexible," White said
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Think of optical fibers, for example: glass windows are hard, but you can wrap a glass fiber around your finger
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Acrylic can be very hard , but in the micropump, the acrylic scaffold was able to be compressed by the beating cardiomyocytes
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"

The scale of the pump suggests, Chen said, "with better printed structures, you may be able to create more complex cellular organization than we had previously imagined
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" Currently, he says, when researchers try to create cells, either Heart cells or liver cells, they're all disordered -- "to get structure, you have to cross your fingers and hope these cells create something
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" This means that the tissue scaffolds pioneered in the micropumps have outside the heart Huge potential implications, laying the groundwork for other organs-on-a-chip, from kidneys to lungs
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In addition to giving us the opportunity to study disease and pathology in human heart muscle, the work paves the way for the creation of cardiac patches that could eventually be used in those who currently have heart defects
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Christos Michas, M.
Çağatay Karakan, Pranjal Nautiyal, Jonathan G.
Seidman, Christine E.
Seidman, Arvind Agarwal, Kamil Ekinci, Jeroen Eyckmans, Alice E.
White, Christopher S.
Chen.
Engineering a living cardiac pump on a chip using high-precision fabrication .
Science Advances , 2022; 8 (16)