Bioprinting: A Revolution in the Making

Since the discovery of penicillin in the early 1900s, average life expectancy has been increasing at a steady rate. Given the recent focus on healthy eating habits and lifestyle choices, it is expected that, within just a few decades, most humans will live longer than one hundred years.

Until now, exploring ways to extend human lifespan has mainly been the purview of academic research labs. In recent years, however, we have witnessed significant investment from the corporate and private sectors in this arena. And given this increased focus and pace of activities in the field, it is not unreasonable to expect that our life expectancy, which has doubled over the last hundred years or so, will increase dramatically again over the next couple of decades.

As we continue to persevere to extend human life, a key concern is organ failure. This issue is akin to the example of car and spark plug. A car that is otherwise fully operational cannot operate if its spark plug is broken. Human organs tend to suffer a gradual loss of function with time. At least a portion of the function may be restored through invasive surgical procedures. However, complete organ failure is inevitable and often irreversible. End-stage organ failure is a major cause of death worldwide, so strategies to replace or fix damaged organs will pave the way for longer lives.

What are our options?

One strategy to combat the issue of death due to end-stage organ failure is organ transplantation, which seems quite straightforward, at least in theory, but is fraught with challenges. A car with a broken spark plug can be restored to normal function by purchasing a new spark plug or salvaging a spark plug from an unused or non-functional car, but because organs are not an off-the-shelf product, we currently rely on organ donations from cadavers or living patients for the transplant. This complicated procedure creates its own concerns—success rate for the operation, risk of immune response potentially leading to organ rejection. Most problematic, there are not nearly enough organs available to meet the current demand, and every year the shortage of human organs for transplantation grows worse. In the past twenty years, the waiting list for organ transplant more than doubled, from about 50,000 to over 120,000. As a result of this shortage, the number of deaths while on the waiting list has also been steadily increasing and is now approximately 8,500 deaths a year. That's about 23 deaths a day! Organ transplantation is not quite the silver bullet we were hoping for.

Another set of options available to humans to replace damaged tissues and organs are medical devices and implants. Examples include hip and finger joints, insulin pumps, artificial heart valves, and even mechanical devices that can replace the entire heart. These are readily available, off-the-shelf products. They save lives and have improved the quality of life for millions worldwide. In spite of these advantages, however, pitfalls abound. It is important to remember that device materials are synthetic. They do not have an immune system to fight off bacteria. Nor can they talk to the body or induce self-repair. There is a growing patient safety concern regarding medical devices, and every year thousands are recalled. For these reasons, it is not clear if medical devices can ever replace natural tissue.

Yet another possibility is to use animal organs for transplantation, and several commercial firms are considering this option. Pigs are currently thought to be the best candidates for organ donation. They are readily available and their organs are comparable in size to humans. However, there are some issues here as well. The immune response for xenotransplantation is generally more extreme than in human-to-human transplants. To date, all transplantation trials have ultimately resulted in rejection of the xenograft, and in some cases even in the immediate death of the recipient. Using animal organs also raises ethical issues and social concerns. A third of the world’s population would not tolerate a pig part as a transplant, due to religious reasons. There are also a number of groups that assert pigs are highly intelligent animals that should not be sacrificed for human use.

So what now? Assuming organ transplants take care of 30-35 percent of patients, and medical devices take care of another 15-20 percent (very optimistic estimates), what are we going to do about the other 50 percent? How are we going to help over 50,000 patients who are on the waiting list with a life-threatening complication? Is there another solution?

A Possible Solution

The short answer is "maybe." Tissue engineering is the bioengineer’s solution to the problem. Simply put, tissue engineering combines principles from engineering, materials science, and cell biology to reconstruct tissues from basic units and replace diseased or injured organs. Since tissue engineering depends on cell biopsies and not whole organ donations, it promises the potential to impact significantly more patients compared to traditional organ transplantation. 

Here’s how it is done: The first step is to obtain donor cells from the tissue of interest, such as the skin, liver or heart and expand them ex vivo. At the same time, a material scientist can develop the biomaterial scaffold for cell incorporation. These two components can then be allowed to integrate in a bioreactor that would provide the cells with the necessary nutrients to start growing the organ (organogenesis). Finally, the biological substitute is implanted into the human body.  

Seems easy, right? Well, not really; it is not straightforward to reproduce the intricacy of tissues and organs ex vivo. Organs are not bags of cells; rather they are sophisticated and complex arrangements of cells and tissues.

Enter the bioprinter

This is where bioprinting comes in. Bioprinting provides an automated and advanced platform to fabricate various organ substitutes through precise deposition of cells and polymers in a premeditated fashion. Bioprinting resembles traditional 3D printing in many ways, but instead of printing plastic or metal, a bioprinter prints bioink composed of cells and hydrogels in intricate, predetermined patterns to create tissue substitutes.

Hydrogels networks of naturally derived or synthetically produced polymers with high water content. They enable efficient absorption of nutrients and oxygen and diffusion of waste and therefore serve as a suitable environment for ex vivo cell culture. Recent breakthroughs in combinatorial synthesis, rapid screening, and computational modeling for the development of biomaterials have helped identify several hydrogels with optimum performance characteristics for bioprinting.  

Human cells represent the bio-active component of the bioink and the choice of the cells used for bioprinting requires careful deliberation. While it seems the choice of cells should be an easy one to make—one would use cardiomyocytes for fabricating heart tissue, neural cells for brain tissue, endothelial cells for vascular grafts, etc.—these cells are derived from primary tissue and hence do not represent an infinite source of cells. On the other hand, stem cells provide the potential to serve as an infinite source of cells for bioprinting. They are capable of proliferating in culture and give rise to unlimited quantities of cells of the same type, they can also differentiate and develop into many different cell types in the body. Recently, several research groups have validated the utility of stem cells in bioprinting, alleviating the need for donor tissue and organs for transplantation. Their research also highlighted the utility of the bioprinted stem cell constructs to model disease and test pharmaceuticals.

How do we move the needle on this?

Before bioprinting can become mainstream, technical challenges as well as ethical and societal concerns involved in the technology need to be addressed. Issues related to high costs and technical barriers have limited the access of the bioprinting technology to elite research institutes and private companies. As a result, a large number of R&D commercial labs and academic institutes, as well as scientists and researchers are not able to access the technology. As with most exponential technologies, it is important to empower a large community of users early on to accelerate the innovations as well as its adoption.

New technologies, especially those related to healthcare, require millions and sometimes billions of dollars of research and development. Therefore, the first implementations are often quite expensive. Questions arise: How will the poor afford it; or will it only be available to the rich? It is important to remember, however, that the cost of any new technology is likely to drop as it advances. Just 10 years ago, it cost $100 million to sequence an entire genome. Today, whole genome sequencing is commercially available for less than $10,000, and several companies are racing to get the cost below $1,000 within the next few years. Similarly, the past decade has already seen an exponential reduction in the bioprinting hardware price, and we can expect that bioprinters will be just as common as traditional 3D printers and will be widely accessible to the scientific community.

Beyond the issues of cost and access, other ethical issues are relevant to consider. Is this technology going to be truly safe for humans? What models will we choose to explore the safety of the bioprinted organs? More importantly, are we going to restrict the use of the technology to benefit human sustenance or will we use this novel technology to build better humans? Replace some organs with a new one that supersedes the earlier? Fabricate a better muscle tissue that does not fatigue easily?

Though these questions must be considered, the technical concerns need to be addressed before the ethical and societal issues. Current statistics for patients with heart disease and other life threatening conditions who require an organ or tissue transplantation clearly delineate the gravity of the situation and the consequences of not intervening with new technologies. It is vitally important to pave the path for this novel technology to become fully operational and effective.

It is equally important to empower the next generation of scientists and engineers with the tools and skillsets related to bioprinting, so that they may participate in the solutions to come. Encouragingly, there has been an increase in efforts to introduce this innovative technology into the high school and higher education curricula.   

What are we waiting for?

The stage is primed and ready for the adoption of bioprinting as a means of addressing the problem of organ failure. There are already numerous ongoing endeavors to develop tissue substitutes for disease models, drug discovery, and testing pharmaceutical and cosmetic products. There are even groups that are looking to bioprint synthetic meat. It will not be long before a bioprinted organ will be available for transplantation.

Bioprinting will revolutionize healthcare. It is the path toward generating patient-specific organs and the solution to donor scarcity. The time is now to make it happen.

Content from this article was originally presented at the Singularity University, where Dr. Prashanth Asuri presented his thoughts on how bioprinting can revolutionize healthcare by creating an abundance of organs for transplantation. Dr. Asuri is an Associate Professor of Bioengineering and Director of the BioInnovation and Design Lab in the School of Engineering at Santa Clara University. He also serves as the co-founder at SE3D, a start-up that develops desktop 3D bioprinters for research and education.