Swirled cardiomyocytes
Heart tissues, unlike other organs, are not able to regenerate, so bioengineers from various laboratories strive to create a whole heart for transplantation. To do this, they must first reproduce the unique microstructure of the myocardium, including the spiral geometry that provides twisting motion during cardiac contraction. For a long time it was assumed that this twisting gives the greatest impetus to pumping blood, but it was difficult to prove this, partly because the creation of hearts with complex architecture was impossible.
A research group of Harvard School of Engineering and Applied Sciences named after John Paulson (SEAS) developed the first biohybrid model of the ventricles of the human heart with spirally arranged cardiomyocytes and showed that this position of muscle cells significantly increases the amount of blood that the ventricle can push out during contraction.
Diagram of the spiral arrangement of cardiomyocytes.
This became possible thanks to a new method of fabric production – Focused Circular jet Spraying (Focused Rotary Jet Spinning, FRJS), which helped to create spirally oriented polymer fibers with a diameter of several micrometers to hundreds of nanometers.
In the first stage, FRJS resembles the production of cotton candy: a liquid polymer solution is loaded into a tank and pushed through a thin hole by centrifugal force when the device rotates. When the solution leaves the tank, the solvent evaporates and the polymers harden to form fibers. The focused airflow then controls the orientation of the fibers as they are deposited onto the collector. The group found that when the collector is tilted, the fibers in the flow will twist around it during rotation, simulating the spiral structure of the myocardium. The human heart consists of several layers of spirally arranged cardiomyocytes with different angles of inclination. The orientation of the fibers can be changed by changing the angle of inclination of the collector.
Two-chamber model of the heart.
Unlike 3D printing, which slows down as the size of the elements decreases, FRJS can quickly spin fibers at a scale of one micron.
In the second stage, the ventricles were seeded with rat cardiomyocytes or cardiomyocytes grown from human stem cells. After about a week, the frame was covered with several thin layers of contracting tissue, and the cells followed the direction of the polymer fibers. The beating ventricles mimicked the same twisting movements that are characteristic of the human heart.
The researchers compared contractions, the rate of transmission of electrical impulses and the ejection fraction between ventricles made of spirally aligned fibers and ventricles made of fibers arranged straight. They found that in each experiment, the spirally aligned tissue outperformed the control.
The group demonstrated that production could be scaled to the size of a real human heart and even larger, but they did not plant cells in large models, since this would require billions of cardiomyocytes.
Article by H.Chang et al. Recreating the heart's helical structure-function relationship with focused rotary jet spinning is published in the journal Science.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru Based on Harvard John A. Paulson School of Engineering and Applied Sciences: A major step forward for organ biofabrication.