The first biohybrid model of human ventricles with beating cardiac cells that are helically aligned has now been created by bioengineers from the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), and it has demonstrated that muscle alignment does, in fact, significantly increase the amount of blood the ventricle can pump with each contraction.
Because the heart, unlike other organs, cannot heal itself after injury, heart disease—the top cause of mortality in the U.S.—is particularly lethal. For this reason, tissue engineering will be crucial for the development of cardiac medicine, ultimately leading to the mass production of a whole human heart for transplant.
The first biohybrid model of a human ventricle with beating cardiac cells that are helically aligned was created by bioengineers, and it has been demonstrated that muscle alignment does, in fact, significantly enhance the amount of blood that the ventricle can pump with each contraction.
Researchers need to duplicate the distinctive structures that make up the heart in order to construct a human heart from the ground up. This includes re-creating helical geometries, which cause the heart to beat in a twisting pattern. It has long been hypothesised that this twisting action is essential for pumping blood at high rates, but establishing this has proven problematic, in part because designing hearts with various geometries and alignments has proven difficult.
“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 Parker, senior author of the paper.
Focused Rotary Jet Spinning (FRJS), a novel additive textile manufacturing technique, allowed for the high-throughput manufacture of helically aligned fibres with diameters ranging from several micrometres to hundreds of nanometers, which enabled this development. FRJS fibres, which direct cell alignment, were created at SEAS by Kit Parker’s Disease Biophysics Group, enabling the development of controlled tissue engineered structures.
The research was published in Science.
“The human heart actually has multiple layers of helically aligned muscles with different angles of alignment,” said Huibin Chang, a postdoctoral fellow at SEAS and co-first author of the paper. “With FRJS, we can recreate those complex structures in a really precise way, forming single and even four chambered ventricle structures.”
A single micron, or around fifty times smaller than a single human hair, is the smallest scale at which FRJS can quickly spin fibres. Consider the extracellular matrix protein collagen, which is also one micron in diameter and is found in the heart. To 3D print the whole amount of collagen in the human heart at this resolution would take more than 100 years. In a single day, FRJS can complete it.
The ventricles were spun before being implanted with rat or human stem cell derived cardiomyocyte cells. The scaffold was covered in several thin layers of beating tissue after about a week, with the cells aligning themselves according to the fibres below. The twisting or wringing motion that characterises human hearts was replicated by the beating ventricles.
Researchers examined ventricles created from helical aligned fibres versus those made from circumferentially aligned fibres in terms of ventricle deformation, electrical signalling speed, and ejection percent. They discovered that the helically aligned tissue performed better than the circumferentially aligned tissue on every front.
The scientists also showed that the procedure could be scaled up to the size of a real human heart and even larger, to that of a Minke whale heart (they didn’t seed the larger models with cells because it would require billions of cardiomyocyte cells).
The team investigates additional uses for their FRJS technology, including as food packaging, in addition to biofabrication.