Reports from the Heart of the Machine
Machine Heart Editorial Department
The human heart can beat without signals from the brain, a property unique to the hearts of advanced animals, which are produced in a specialized set of cells that produce periodic electrical oscillations and mechanical feedback, the mechanism of which is not fully understood.
Although the exact mechanism of the heart's pacing action is not known, can we build a "heart" of ourselves to replicate this physical process? There are scientists who have done it.
Today's protagonists are "fish" that are bouncing around alive.
The fish wanders around in a glucose salt solution, its tail rhythmically swinging from side to side. It may be hard for you to believe that this swing comes from the beating power of the human heart.
This is a "synthetic fish" device developed by scientists at Harvard and Emory Universities, which is made up of living cardiomyocytes (grown from human stem cells) that can swim for more than 100 days. The research was featured in the top academic journal Science.
Address: https://www.science.org/doi/10.1126/science.abh0474
The creation of this synthetic fish is based on two key regulatory characteristics of the human heart: (1) the heart acts spontaneously without the need for conscious input (automaticity) ;(2) the transmission of information initiated by mechanical movement (mechanical electrical signals).
The experience gained from this study helps researchers study heart disease in more detail. Kevin Kit Parker, a biological engineer at Harvard University and one of the authors of the paper, said: "The ultimate goal of the study is to build artificial hearts to replace malformed hearts in children."
Creating something that looks structurally and heart-like is relatively easy, and making a model that actually functions like a heart is a daunting challenge. The creeping fish-shaped robot is a big step toward that goal, building on two previous studies using rat cardiomyocytes, one to build an artificial jellyfish and the other to a cyborg stingray.
"I can build a model heart with Play-Doh, but that doesn't mean I can build a heart." Parker said. It is relatively easy to grow other cells, but it is not possible to summarize the physical properties of a system that beats more than 1 billion times over the human life cycle by designing to use other cells.
This is where the key issue of the challenge lies. The synthetic fish research using human heart cells is to open a breakthrough in this problem.
What does a "fish" made from heart cells look like?
Let's start with the construction of this synthetic fish.
In terms of design, on the one hand, this fish has a double layer of muscle cells, one on each side of the tail fin. When one side shrinks, the other side stretches, which opens the channel of ions sensitive to mechanical motion, causing charged ions to flow in and contract on that side.
Overall, the fish is made up of 73,000 living cardio myocytes (CM), with a total hydrogel paper complex of 14 mm in length and a total mass of 25.0 mg, including 0.36 mg of muscle mass.
The image below details the fish's five-layered body structure. When one side of the fin contracts, the other side stretches, creating a self-sustaining swimming movement.
On the other hand, the researchers also designed an "autonomous pacing node," which they call G-node, which, like a normal pacemaker, controls the frequency and rhythm of autonomous contraction. Together, the two layers of muscle and the autonomous pacemaker node produce continuous, spontaneous and coordinated back and forth fin movements that can drive the fish to swim for more than 100 days.
Considering the synthetic fish's autonomic antagonistic muscle contractions, the researchers explored how this autonomous movement could improve its long-term performance. The results showed that the synthetic fish remained autonomous for 108 days, equivalent to 38 million beats. In contrast, the cyborg stingray lasted only 6 days, and the skeletal muscle-based synthetic actuator lasted 7 days.
Figure 5A below shows the trajectory of synthetic fish (mesh 1cm), 5B is the swing angle of a 108-day synthetic fish with 79% antagonistic contraction, and 5C is the swimming performance of synthetic fish over 108 days. Synthetic fish equipped with bilayer muscle cells showed increased contraction, maximum swimming speed, and muscle coordination in the first month, and maintained their performance for 108 days.
This also means that, unlike other biological robots, this synthetic fish will continue to improve its performance as we age. As cardiomyocytes mature, the fish's muscle contraction intensity, maximum swimming speed, and muscle coordination increase in the first month, eventually reaching a speed and efficiency similar to that of wild zebrafish.
Specifically, synthetic fish swim faster (15.0 mm/s) than previously biomixed muscle systems. This rate is 5 to 27 times faster than that of cyborg stingrays, highlighting the importance of feedback mechanisms in the development of biomixing systems. And, when considering the ratio of muscle mass to total body weight in synthetic and semi-mechanical stingrays, the synthetic fish swims an order of magnitude faster per unit of muscle mass than the cyborg stingray, 13 times the latter's maximum speed.
Figure 4 below compares the maximum swimming speed between mixed "fish" and wild fish of different organisms. It can be seen that the maximum speed of this synthetic fish exceeds that of juvenile zebrafish and white Morley, among others.
Future outlook
"By harnessing the heart's mechanical electrical signals between the two layers of muscle, we reconstructed the cycle that each contraction automatically generates as a response to stretching on the other side," says Keel Yong Lee, a biological engineer at Harvard University, a co-author of the paper. "The results demonstrate the role of feedback mechanisms in muscle pumps such as the heart."
The researchers also integrated a pacemaker-like system into the biological mixture to form an isolated cluster of cells capable of controlling movement frequency and coordination.
"Thanks to these two internal pacing mechanisms, our fish can live longer, move faster, and swim more efficiently." A co-author of the paper, Georgia Tech, Emory University Wallace H. Sung-Jin Park, an assistant professor in Kurt's Department of Biomedical Engineering, said.
The microstructure of the semi-mechanical, semi-biological fish shrinks in size as the zebrafish it imitates – a purely mechanical robotic system that can propel itself forward more effectively.
"Unlike research that uses heart tissue as a blueprint, we identified the key biophysical principles that make the heart work, used them as design criteria, and copied it into a system—a living, swimming 'fish, which makes it easier to see if we succeed." Sung-Jin Park said.
Mathias Gautel of King's College London said: "If the study goes well, the fact that primary cells isolated from the animal's true heart could possibly survive for two to four weeks, or even extend it to the level of the entire life cycle of small animals, is amazing."
In the future, the team will use human heart cells to build more complex biomixing devices.
Reference Links:
https://bme.gatech.edu/bme/news/researchers-create-biohybrid-fish-powered-human-heart-cells
https://www.sciencealert.com/watch-this-biohybrid-fish-swim-to-the-rhythm-of-its-living-human-heart-cells
https://www.newscientist.com/article/2307975-robofish-powered-by-human-cardiac-cells-gives-fresh-insight-into-heart/