Researchers at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) report that they have developed a biohybrid model that reconstructs the heart muscles’ helical structure, taking them a step closer to fabricating artificial human hearts.
Heart disease is a major cause of death in America. This is, in part, because the organ lacks the ability to repair itself following an injury, unlike others.
Tissue engineering is deemed critical for notable advancements in cardiac medicine. Scientists hope that it will lead to the development of hearts for transplants, but this has proven impossible so far.
The heart is a complex organ. A helpful artificial variant needs to be able to replicate its distinctive structures, including its helical geometries.
For centuries, scientists have posited that the helical structure of the heart’s muscles is central to the organ’s high-volume blood-pumping action. They have, however, found it hard to prove this.
The newly-developed biohybrid model of human ventricles, which helically-aligned beating cardiac cells, therefore, represents a major breakthrough. Researchers were able to show that the alignment of muscles hugely boosts the blood-pumping action of the ventricle.
“This work is a major step forward for organ biofabrication and brings us closer to our ultimate goal of building a human heart for transplant,” said senior study author Kit Parker, SEAS’s Family Professor of Bioengineering and Applied Physics.
The SEAS bioengineers published their breakthrough in the journal Science.
Centuries-old mystery
The idea underlying this novel biofabrication process has been around for hundreds of years. Back in 1669, English physiologist Richard Lower observed in his book Tractatus de Corde how the muscles of the heart were set like spirals.
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Researchers have since confirmed the helical structure of the heart’s muscles. However, they have struggled to fully understand the rationale behind the twisting muscles.
Edward Sallin, a past chair of the University of Alabama Birmingham Medical School’s Department of Biomathematics, posited in 1969 that the heart’s helical structure was intended to significantly enhance the amount of blood that ventricles pump with every contraction.
The authors of this paper, therefore, set out to look into Sallin’s hypothesis. They wanted to find out the impact of the helical structure of the heart’s muscles.
New biofabrication method
The bioengineering researchers tested Sallin’s argument and developed their biohybrid model using a Focused Rotary Jet Spinning (FRJS) system. This new technique of additive textile manufacturing enabled researchers to fabricate helically-aligned fibers, similar to the heart’s muscles. The diameters of these fibers range from a few micrometers to hundreds of nanometers.
Using centrifugal force, the FRJS system ejects a liquid polymer solution through a small hole as it spins. The liquid solution becomes solid to form fibers as they exit the reservoir holding them and as the solvent evaporates.
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The team used a focused airstream to control the fibers’ orientation and then deposit them on a collector. By manipulating the shape and turning of the collector, the fibers aligned and coiled around the mold while spinning to form a helical structure.
“The human heart actually has multiple layers of helically aligned muscles with different angles of alignment,” said co-first author Huibin Chang, a bioengineering research associate at SEAS. “With FRJS, we can recreate those complex structures in a really precise way, forming single and even four chambered ventricle structures.”
Researchers suggested that FRJS is a massive improvement on what’s possible with 3D printing. It does not become slower as features get tinier, unlike the latter. For example, more than 100 years would be needed to 3D print every piece of collagen in the heart. FRJS can finish that job in just a day.
The bioengineers seeded devised ventricles with cardiomyocyte cells from rats or human stem cells. These were covered with threadlike layers of beating tissue in just about a week as a result and displayed properties similar to those of a real human heart.
Also, the team compared ventricles formed from helically aligned fibers and those from circumferentially aligned fibers. The former was found to trump the latter in all regards.
This paper provides a proof of concept for how to approach the engineering of tissues and organs with complex geometries. The researchers said this method could be used to make a heart as large as that of a minke whale. They are also exploring other possible applications, including food packaging.
Read Also: Organ Transplantation: Researchers Change Blood Type A Donor Lungs to Universal Type O Blood Lungs
References
Recreating the heart’s helical structure-function relationship with focused rotary jet spinning
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