Researchers at Harvard’s John A. Paulson School of Engineering and Applied Sciences (SEAS) believe they’ve made a step toward solving an age-old heart muscle mystery — and toward the ability to eventually fabricate whole human hearts. for transplant.
Using a new form of fabric manufacturing, similar to a cotton candy machine, the SEAS team was able to build a model of human ventricles (those fleshy chambers in the heart that pump blood into the body) that could not only beat, but have the unique heart muscle structure recreated – a structure scientists have been trying to understand ever since 1669.
“This work is a major step forward for organ biofabrication and brings us closer to our ultimate goal of building a human heart for transplantation,” said Kit Parker, the study’s senior author and SEAS professor of bioengineering. and applied physics.
Heart muscle is not laid out in neat lines like a French mime’s shirt. Instead, it forms a kind of spiral, the final purpose of which has been a mystery to science since the 17th century.
A broken heart: The ability to bioprint a human heart is one of the holy grails of cardiac medicine, as the heart – unlike many other organs in the body – does not repair itself after an injury, such as a heart attack.
Recent research with gene therapy and microRNA technology has enabled scientists to regenerate heart muscle in pig hearts, a good model for humans, while other research groups are still racing to build hearts for transplant.
To do that, however, we need to be able to mimic the structures of the heart. That includes a structural feature called “helical alignment” that researchers have been puzzling over since the 17th century.
A heart muscle mystery: Heart muscle is not laid out in neat lines like a French mime’s shirt; instead it forms something of a spiral. This spiral alignment creates a twisting motion when it pumps.
The spiral alignment was first characterized by the English physician Richard Lower in 1669 in his book Tractatus de Corde – a real work of the heart, literally. The trailblazing cardiovascular researcher wasn’t sure Why however, the heart muscle spiraled and 300 years of research had yet to find the definitive answer.
In a nice bit of poetic symmetry, Edward Sallin of the University of Alabama Birmingham Medical School put forward a theory in 1969: that the spiral heart muscle helps the heart pump more blood with each beat, making it the most efficient heart design.
So why don’t we know if Sallin is right fifty years later?
“Testing this possibility is difficult, however, because it is challenging to reproduce the fine spatial features and complex structures of the myocardium using current techniques,” the SEAS researchers wrote in their study, published in Science.
The Harvard team set out to make it happen.
“Our goal was to build a model that would allow us to test Sallin’s hypothesis and study the relative importance of the helical structure of the heart,” said John Zimmerman, postdoc and co-first author of SEAS.
heart cotton candy: The SEAS team used a recently developed process from Parker’s lab called Focused Rotary Jet Spinning (FRJS) to create their heart model.
The researchers describe FRYS as comparable to a cotton candy machine. The device spins and forces out a polymer that can be adjusted using an airflow. By tilting and twisting it, the team found they could form scaffolds that mimic the spirals of the heart muscle.
“The human heart actually has multiple layers of spirally aligned muscles with different alignment angles,” said Huibin Chang, postdoctoral researcher and co-first author of SEAS. “With FRYS, we can recreate those complex structures in a very precise way, forming single or even four-chambered ventricular structures.”
The team created spiral scaffolds in the shape of ventricles, after which the heart muscle cells of rats and humans spread out, like a pet heart chia, growing multiple thin layers of beating muscle tissue.
Using their new technique “we can recreate those complex structures” [of the heart] in a very precise way, forming ventricular structures with one or even four chambers.”
The model ventricles beat with the same twisting motion as a real human heart, which the team found could pump blood better from the ventricle — a measurement known as ejection fraction — to support Sallin’s theory.
The researchers were able to use FRYS to create larger heart models, from a human to a mining whale, even though they didn’t coat them with the billions of cells they needed to grow beating tissue.
In addition to providing a model of the spiral heart muscle to study, the researchers believe their work could help improve the biofabrication of hearts for transplants, and even for applications outside of medicine, such as food packaging.
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