Biomedical engineers at the University of Toronto have developed a method to create a small-scale biosynthetic left ventricle that can pump blood within a bioreactor. While the construct is too small to act as replacement for a human heart, it could lead to full-sized biosynthetic organ transplants. In fact, the man-made ventricle already showed a significant level of sophistication and biomimicry with a multilayered structure and the ability to pump blood. In the meantime, the artificial construct can help researchers to better understand heart disease and test new treatments. The researchers created it by seeding cardiac cells onto a flat scaffold and then rolling it around a tube, creating a multilayered construct that can beat spontaneously.
Replicating the natural complexity and sophistication of our organs in the lab is no mean feat. However, the potential rewards are enormous – imagine a world with no transplant waiting lists and the ability to grow a custom organ using your own cells that is perfectly primed to replace a diseased organ within your body. While there is likely a relatively long road before we reach this point, there are certainly some interesting milestones along the way.
This latest method to create a biosynthetic ventricle is one such milestone. This approach makes an effort to replicate the layered nature of the heart wall. “Until now, there have only been a handful of attempts to create a truly 3D model of a ventricle, as opposed to flat sheets of heart tissue,” said Milica Radisic, a researcher involved in the study. “Virtually all of those have been made with a single layer of cells. But a real heart has many layers, and the cells in each layer are oriented at different angles. When the heart beats, these layers not only contract, they also twist, a bit like how you twist a towel to wring water out of it. This enables the heart to pump more blood than it otherwise would.”
To achieve a multilayered ventricle, the researchers started with a flat biocompatible polymer scaffold that they seeded with cardiac cells. The scaffold contained three panels with grooves aligned at different angles, which helps to recapitulate the twisting motion of the heart when the ventricle is fully assembled. Once the cardiac cells had settled on the scaffold and began growing, the researchers wrapped it around a hollow tube, forming a multilayered structure that can beat spontaneously and pump blood in a bioreactor system.
“Our model has three layers, but a real heart would have eleven,” said Radisic. “We can add more layers, but that makes it hard for oxygen to diffuse through, so the cells in the middle layers start to die. Real hearts have vasculature, or blood vessels, to solve this problem, so we need to find a way to replicate that.”
Here’s a video schematic of the fabrication process:
Study in journal Advanced Biology: Toward Hierarchical Assembly of Aligned Cell Sheets into a Conical Cardiac Ventricle Using Microfabricated Elastomers