Article by Roberta Lock & Richard Z. Zhuang
3D Printing an Anatomically Correct Human Heart
3D Printing of Personalized Thick and Perfusable Cardiac Patches and Hearts, Advanced Sciences, 2019
Nadav Noor et al., Tal Dvir Lab
One of the biggest goals of heart tissue engineering is to be able to engineer a fully functional human heart in the lab. However, one of the biggest challenges we face today is being able to recreate the heart’s complex architecture. With four unique chambers, a valve system, and a network of blood vessels underlying the entire organ, the heart is one of the most structurally complex organs in the body. This research shows that 3D-printing technology has the potential to overcome this obstacle, and bring us closer towards creating fully engineered organs.
What did the researchers do?
Researchers 3D printed beating heart patches that matched the anatomical structure, cell composition, and biochemical properties of a patient's heart. Additionally, as a proof-of-concept for 3D printing large and complex structures, they also generated a small-scale human heart with the basic anatomical structures (four heart chambers and major blood vessels).
3D-printed miniature heart by T. Dvir Lab
Why is this important?
The main goal of creating a cardiac patch is to transplant it onto a human heart to help replace damaged or injured heart tissue. However, to do this, cardiac patches would need to be much thicker and stronger than they are now. Generating large-scale heart tissues is one of the largest challenges in cardiac tissue engineering.
To function properly, cells need nutrients and oxygen, and the cells of the heart are especially demanding. In the body, these nutrients are delivered by the blood vessels (vasculature), which efficiently ensure all cells receive the necessary oxygen and nutrients, and remove waste products. In engineered cardiac tissues, this vasculature isn’t naturally present. This means if a tissue is too large, the center of it doesn’t receive enough oxygen and the cells die (we call this a “necrotic core”). With 3D printing, endothelial cells (which form blood vessels) can be placed in networks throughout the tissue to from vasculature. These blood vessels allow for nutrients to flow throughout the cardiac tissues and thus allows us to overcome the size limitations.
How did they achieve this?
A sample was taken from a fold of fatty tissue surrounding the stomach of a patient. The cells from the tissue were reprogrammed into stem cells, which were then turned into the cell types necessary for heart muscle (cardiomyocytes, which are the muscle cells that beat, and endothelial cells, which form blood vessels). The non-cellular part of the patient sample, the extracellular matrix, was processed into a supporting biomaterial to encapsulate the cells, called a hydrogel. The two cell types were combined with the hydrogels to form “bioinks” for 3D printing. The cells are then 3D printed into a heart patch, following a blueprint created by imaging the patient’s heart, allowing the patch to match the anatomical structure of the patient’s own heart.
What comes next?
3D printing is a promising approach for engineering whole organs like the heart, but many challenges still remain.
How long will the heart patch last? The heart patch must be tested for much longer periods of time to evaluate its safety and effectiveness. This is usually done in small animal models, like rats and mice.
Is the vasculature good enough? The technology for 3D printing blood vessels is still limited. While the basic structures can be created, printing the smaller blood vessels within large tissues still must be developed in order to create efficient nutrient flow to all cells in the construct.
Can we make the patch bigger? Another challenge with making larger heart tissues is we need the cells to make it! In the human heart, there are 2-3 billion cardiac muscle cells alone (and that’s less than ⅓ of the total cell number in the heart). Cultivating huge numbers of cells simultaneously is very difficult and expensive to do. Methods to scale up cells to these high numbers are still being optimized.
What about the 3D printed anatomically correct heart we see in this paper? The 3D printed small-scale heart shown in this paper is really cool, but there’s still a long way to go before it’s functional. This heart was printed into a gel for support, since it would currently collapse under its own weight. This is an incredible proof-of-concept showing how 3D printing can achieve such complex tissue designs, but figuring out how to make that tissue functional is a future challenge.