I remember that around April last year, researchers at Tel Aviv University successfully “printed” the world’s first 3D vascularized heart using patients’ own cells and biomaterials, and the first time a complete heart filled with cells, blood vessels, and ventricle had been designed and printed. A year later, how far has the world’s 3D-printed heart gone?
Unlike other organs, the heart is functional because of its large size, wide variety of cells and the need for autonomous beating. Even though 3D printing technology has been developed for many years, it is still very difficult to print a heart that matches the patient’s cytology, biochemistry, anatomy, and so on in the medical field, such as cranial maxillofacial surgery, orthopaedics, and oral medicine, and so on.
Where is the 3D-printed heart difficult?
3D-printed heart is not as simple as stacking a pile of cells into the heart. First, we know that the heart’s neat beating requires a close connection between the heart’s cells, and that the presence of Earth’s gravity, directly or indirectly, makes all this impossible. The 3D-printed heart cannot pump blood because the heart cannot beat neatly.
Not only that, unlike other 3D printing commonly used lasers or heat, since bio3D printing uses cells, there can be no light and heat to ensure cell activity. Bio3D printing according to different cell growth environment, need to set the printing parameters, accurately control the density of cells in biological materials, growth factors in the overall 3D structure of the position and related role, in order to make the printed tissue biological activity.
Plus the heart is more complex than the average organ — it beats. The heart muscle cells are tightly connected, the electrical signals produced by the cells will cause a large number of heart muscle cells to contract together, in order to coordinate the co-shrinkage of two atriums and two ventricle, the heart itself has a special conduction system. Although it’s not hard to produce tens of millions of heart muscle cells in vitro, even if the heart is 3D printed, it’s one thing to jump, and another.
As far as clinical conditions are concerned, ventricular fibrillation is because heart muscle cells can not jump synchronously, once the loss of “synchronization”, each cell jumps from time to time will let the heart in an instant loss of pumping function, resulting in the death of patients. Therefore, if the heart’s pumping function is to be achieved, the heart must beat very neatly.
Whether the printed heart can beat neatly is actually related to the gravity of the earth. 3D-printed adhesion is not strong enough to support large organs such as the heart or kidneys, which can cause tearing between cells under the influence of gravity. Therefore, the core problem of bio3D printing is how to solve the effects of biological materials and Earth gravity on 3D printing cells.
To what extent has the world’s 3D-printed heart reached?
Although there have been no successful transplants of full 3D bioprinted hearts, this has not affected the progress of biopharmaceutical companies and research teams toward a fully functional 3D-printed heart. Here we’ve also sorted out some of the more promising 3D-printed heart projects of late.
Miniature Heart at Tel Aviv University
Tel Aviv University, as we mentioned at the beginning, its School of Molecular Cell Biology and Biotechnology has successfully produced the world’s first cell with blood vessels and other support structures that can even shrink the 3D-printed heart like the heart. Although the heart is only 2.5 cm long, it is the first time that human cells have been used to completely vascularize the human heart, a key step towards bioprinting of functional human organs.
The technical principle is to extract human cells from the experimenter’s adipose tissue, then transform them into stem cells, and then differentiate the cells into various types of heart cells in the heart, which are mixed with inorganic materials to make bio-inks, which eventually be 3D printed.
Because the patient’s own cells are used, the rejection of new bioengineering organs can be completely eliminated. Be aware that rejection is a major problem in organ transplants, and many patients who receive heart transplants experience rejection symptoms within the first year of surgery. With this success, the team’s next challenge is to mature and function as expected, and hopes that within 10 years, the world’s best hospitals will be equipped with organ 3D printers and will be able to serve patients as normal.
Bioengineered Heart Tissue of WFIRM
Dr. Anthony Atala, director of WFIRM, is well-known in the field of 3D bioprinting. A few years ago, his team engineered and transplanted the bladder to live patients. To date, the Institute has developed more than 30 different tissues and organs.
In April 2018, the WFIRM team published a paper describing the team’s use of rat heart cells 3D bioprinting functional and contractionary heart tissue. These cells are suspended in bio-ink and printed into structures similar to human heart tissue, and can test the effects of hormones such as epinephrine and carbapenem, as in organisms, which can lead to expected changes in heart rate in the printed heart tissue.
Earlier this year, WFIRM announced the creation of a miniature human “model” containing different bioengineered human tissues that will be dedicated to drug testing. Tiny organ structures are about one millionth the size of an adult and include tiny heart tissue. Dr Atala said one of the most important functions of the micro-human laboratory model was to determine whether a drug was toxic to humans early in development, which had a huge impact on experimental drug testing.
Biolife4D Micro Heart
Biolife4D is headquartered in Chicago and aims to create transplantable human hearts using bioengineering and 3D printing technology. In 2018, they successfully demonstrated the biological imprint of a patch of human heart tissue, which means that the tissue has blood flow and can contract like a real heart. These heart tissue patches can be used to restore damaged parts of the heart in patients with acute heart failure.
To produce these patches, they used MRI machines to obtain a 3D digital model of the patient’s heart, using the patient’s own heart cells, combined with nutrients and other biological materials to create bio-ink. Finally, tissue patches are 3D printed and matured in bioreactors until they can be ported.
Last September, the company also announced another major breakthrough, the Mini Heart 3D Printer, made from bio-inks with human heart characteristics, replicating many of the characteristics of the human heart. Biolife4D has also improved its bioprinting algorithm, which is optimized for heart 3D printing. Biolife4D says this new milestone will enable the ultimate goal of a “full-size, 3D-printed functional heart for successful transplantation” simply by optimizing the process and expanding the technology.
Artificial heart valves at ETH sAT
In 2017, a team of researchers at the Swiss university of science and technology, ETH Zurich, published a paper describing the functional beating of the heart, printed in silicone 3D, which is about the same size as the human heart, and that their work is proof that we are rapidly realizing the ability to replace the heart without a transplant.
This silicone-printed body has a left and right ventricle and a chamber that drives pumping movements through compressed air, with the main limitation being that the 3D-printed heart can only last about 30 minutes or 3,000 beats, and the material will then degrade and weaken. By 2019, the team has teamed up with South African company Strait Access Technologies to develop artificial 3D-printed heart valves that can replace leaks or damaged valves in real patients. These components are 3D printed in a body-compatible material and provide the same blood flow function as conventional replacement valves.
For the success stories of artificial heart valves that have been used for transplantation, the artificial heart valves developed by ETH sAT can be tailored to each patient. Thanks to MRI and CT imaging, each valve can be specifically designed for perfect fit.
In fact, every year a large number of patients die while waiting for a heart transplant. Even if a successful transplant is successful, there will be a rejection reaction that triggers postoperative syndrome within a few years of surgery, and these are the implications of our study of 3D-printed hearts, saving more patients, and tackling organ transplant rejection.