It’s been 50 years since Dr. Christiaan Barnard performed the first successful human-to-human heart transplant in South Africa – a procedure that would forever change the way heart disease is treated. Over the last half-century we’ve seen continued innovation in organ transplantation, from tissue typing to the discovery of immunosuppressant drugs, leading to a longer survival rate for transplant recipients.
Still, there is much work to be done. Organ supply falls far short of demand – at any given time there are more than 100,000 Americans alone on the waiting list for heart transplants, with only about 2,000 performed in the U.S. each year – and organ rejection is still a major obstacle the industry must overcome. However there is a promising new technology currently under development – 3D bioprinting – that could change the course of treatment forever.
What is 3D Bioprinting?
3D bioprinting is the process of creating cell patterns in a confined space using 3D printing technologies, thereby preserving cell function and viability within the printed construct. More simply, a 3D bioprinter is a specialized 3D printer developed to protect living cells during printing. Now, bioprinters can create functional biological structures to potentially restore, maintain, improve, or even replace existing organ function.
3D bioprinting may seem like a “next generation” concept, but so too did many medical advancements and achievements throughout the course of human history. In fact, for some time now, scientists and engineers have used 3D printers to create objects from metals and plastics, in an industry projected to be worth nearly $33 billion by 2023. Printing inanimate objects has its use, but what if we could print functional human organs made up of a patient’s own genetic material, creating a perfect match for transplant and eliminating the need for a donor?
How Does It Work?
The 3D bioprinting process – of a heart, for example – begins with magnetic resonance imaging (MRI) creating a detailed three-dimensional image of a patient’s heart. Computer software uses this image to construct a digital model of a new heart for the patient, featuring the original shape and size. After safely extracting cells from the patient through a blood sample, those blood cells are reprogrammed and converted into specialized heart cells, leveraging recent stem cell developments.
The heart is made of several specific cell types, but most of them are cardiomyocytes and the cardiac pacemaker cells. The cardiomyocytes are essentially the muscle cells, and the pacemaker cells produce electricity by rapidly changing their electrical charge from positive to negative and back again.
Next, a “bio-ink” is created using the specialized heart cells, nutrients, and other materials that will help the cells survive the bioprinting process. The bioprinting is then done with a 3D bioprinter – one layer at a time, and with the dimensions from the MRI and the latest resolution capabilities – to create a perfectly sized heart. Since the cells aren’t fused together yet, a biodegradable scaffolding made of one of several materials – like pluronic acid – is printed with each layer to hold it in place. After printing, the heart is matured in a bioreactor, which mimics conditions inside of the human body, where it is made stronger and readied for transplant. The cells self-organize and fuse into networks of living tissue and begin to beat in unison, and the biodegradable scaffolding dissolves. By definition, autonomous self-assembly is the organization of components – from an initial state into a final pattern or structure – without external or human intervention. This is one of the most remarkable parts of the process, as mother nature takes care of it herself.
Through millions of years of evolution, the cells know what to do and how to do it. Each cell has the same DNA, which is the blueprint for everything that individual cells must do and how to do it. This seemingly incredible process of cells communicating and signaling one another is the exact same process that forms everything in our bodies. Everything in the body is made of cells, all of which began as stem cells. Once a stem cell is needed to transform to a specialized cell, the natural biologic process facilities that communication, and the stem cell becomes specialized and functions accordingly. In addition to structure and the proper environment mimicked by the bioreactor, the heart also needs oxygen, nutrients, and waste removal, and vascularization makes all of this possible.
The end result is an entirely new, viable living heart. This process also eliminates the chance of organ rejection, since the transplantable organ is made of the recipient’s own cells, meaning it will be recognized as the patient’s own organ and not as foreign. From cell collection to finish, the entire process takes just several weeks, and the bioprinting process itself is complete in a matter of hours. This has been done in portions, but a full-sized heart viable for transplant has yet to be printed.
Like all innovation in the medical space, there are some challenges before the technology is brought fully to fruition. While the premise for the technology currently exists, there is still a great deal of testing and development that must be done to optimize the process. This requires a significant amount of resources, as well as a leading team of experts within the scientific and medical fields dedicated solely to the advance of the technology.
However, these groups are currently forming, and robust testing and research are well underway. We believe the main challenges are related to scaling up the process and the vascularization details that this involves. Portions of one have been printed, but a full-sized heart viable for transplant has not yet been printed. It is this process we are working on completing. We are hoping to have a “mini-heart” within about a year, and from there it is primarily a scaling process. We will also be working on solutions for less advanced heart disease needs such as heart valves and possibly cardiac patches, both of which would make a huge impact on meeting critical demand challenges for people with lesser advanced stage heart disease.
Second, there is the FDA. The health and medical devices industry is heavily regulated in the United States, so the technology will have to undergo the arduous testing process of the industry’s foremost governing body. But like all innovative procedures and devices before it, once 3D bioprinting is fully evolved, it will be well prepared for testing and to showcase the life-saving benefits it can provide.
Not only with hearts, but with organs as a whole, the transplant-ready supply is well short of the demand. Kidneys and pancreases also create medical complications and are thus logical candidates for 3D bioprinting. By replacing the kidneys of someone in failure who is required to continually get dialysis to live, we would not only be helping save their life but also increasing their quality of life because they would be removed from dialysis. The pancreas brings a similar benefit – if you have type 1 diabetes you are not producing insulin. But if you had a transplanted healthy organ that produces insulin like it should, you will no longer be a type 1 diabetic.
The more the technology matures, the more types of organs it will be able to print, and the more lives it will be able to save. With hundreds of thousands of people dying annually because of the shortfall of available organs, this is not just an opportunity, but a responsibility.
Steven Morris is the CEO of BIOLIFE4D, a pioneering biotech company laser focused on leveraging advances in life sciences and tissue engineering to 3D bioprint a viable human heart suitable for transplant.