By Bertalan Meskó, The Medical Futurist | July 7, 2018
3D bioprinting might be the response for worldwide organ shortages, as well as to the increasing reluctance to test new cosmetic, chemical, and pharmaceutical products on animals. Do you believe that organs grown in laboratories barely exist in sci-fi screenwriters’ heads? Do you think that 3D printing is only used for manufacturing phone cases and plastic toys? It’s high time to set the record straight. Here’s how bioprinting will break into healthcare revolutionizing organ donations and animal testing.
Wait a minute… what is bioprinting?
Put the term bioprinting next to Earth-invader androids, shiny spaceships in a post-apocalyptic setting, and you’ll get the next Hollywood blockbuster. However, opposite to malevolent aliens, bioprinting not only exists in sci-fi movies, all the more it will transform healthcare in the following decades. Before going into details, though, let’s dissect the technology itself.
3D bioprinting means the creation of living tissues, such as blood vessels, bones, heart or skin via the additive manufacturing technology of 3D printing. The latter implies the production of three dimensional solid objects from a digital file using a layering process. In its most common version, a source material, for example, plastic, is liquefied and then the machine adds layer after layer on the platform until you have a fully formed object.
Needless to say, printing organs is a “little bit” more complicated. It was in the early 2000s when researchers discovered that living cells could be sprayed through the nozzles of inkjet printers without damaging them. However, it is not enough to have the cells themselves, they need a nurturing environment to stay alive: food, water, and oxygen. Nowadays, these conditions are provided by a microgel – think gelatin enriched with vitamins, proteins, and other life-sustaining compounds. Moreover, to create conditions fostering the fastest and most efficient cell growth, researchers plant the cells around 3-D scaffolds made of biodegradable polymers or collagen so they can grow into a fully functional tissue.
Bioprinting a bladder
Let’s take the example of the bladder, a simpler organ consisting of only two types of cells. At first, researchers scan the patient’s organ to determine personalized size and shape. Then they create a scaffold to give cells something to grow on in three dimensions and add cells from the patient to this scaffold. That’s painstakingly labor-intensive work and could take as long as eight weeks. Finally, a bioreactor creates the optimal environment for the cells to grow into an organ. When doctors finally place the organ in the patient, the scaffold has either disappeared or disappears soon after surgery.
The description cannot demonstrate how difficult and time-consuming the entire process is, so mass production is definitely further down the road. Synthetic skin, a bionic ear, bladder, or cornea might be the first tissues to be either bioprinted or grown in the lab on demand. After that, more complicated ones might be engineered. We are a long way from bioprinting fully functioning, complex organs, even decades away, but the constant development of tissue engineering will result in more and more applications of synthetic skin, bladder, liver or cornea.
The solution for alarming worldwide organ shortages comes from technology
3D bioprinting is the response of technology to critical tissue shortages hampering the tasks of medical professionals and endangering many lives. In the US, the number of patients waiting for an organ donor have multiplied five-fold in the last 26 years, but the number of donors was only 13 percent of the necessary – although their figures also doubled over the previous two decades. That’s how the tragic situation draws up that on average eighteen people die every day from the lack of available organs in the US.
Other countries are no better off either. According to statistics of the NHS, 429 patients died in 2014 in the UK while on the active waiting list for an organ transplant, 38 of whom were waiting for heart transplants. Australia faces a critical shortage of donated tissue, including skin, bones, heart valves and tendons, while Japan fights a lack of skin tissue saving burn victims. How brutal is it that a patient who needs an organ transplant either has to wait for someone to donate it while alive or dead?
How long do we have to wait for the commercialization of bioprinting?
“The future of bioprinting might look like the Dell model,” thinks Dr. Anthony Atala, director of Wake Forest’s Institute for Regenerative Medicine, one of the most progressive places when it comes to tissue regeneration. For example, James Yoo and his team have developed a prototype that can create synthetic skin.
“Your surgeon will ship your tissue sample to a company. A few days later, the organ will arrive in a sterile container via FedEx, ready for implantation”, he explained. Dr. Atala also emphasized that there are no surgical challenges, only technological ones. If we can overcome those hurdles then engineered tissue can function as the original one.
He believes scientists will one day successfully restore function to damaged, complex organs, either through cell therapies or perhaps by inserting a slice of functioning engineered tissue into the damaged organ. It will take many years of endeavor to come about.
There is hope, though. Specific tissues Dr. Atala said, such as blood vessels, vagina, and urine tubes, have already been grown in the lab and implanted in a small number of patients undergoing clinical trials. Scientists around the world are working to expand the number of tissues that can be engineered and the number of patients who might benefit.
With bioprinting against testing drugs on animals
Another, perhaps less advertised application of bioprinting is how it can help eliminate the need for testing new drugs on animals. Clinical trials today are lengthy and expensive. Pharma companies spend billions of dollars and still, at the end of the day a drug might not become approved. Moreover, testing medication on mice, rabbits or other animals is in many cases not efficient as the particular drug could still have a different effect on people.
On the other hand, 3D printed tissue is proving to be an effective means of testing new pharmaceuticals, meaning that drugs can be thoroughly assessed and brought to market more quickly, all without harming animal test subjects. Moreover, as testing of cosmetics on animals has always been even more controversial than testing for medical purposes, with the emergence of 3D printing human skin, testing cosmetics on animals could disappear once and for all.
The pioneers of bioprinting: Organovo, CELLINK & Co.
Looking at the potential in the technology, no wonder that the market for bioprinting research is rapidly expanding. According to a report by Research and Markets published in June 2018, theglobal bioprinting market will likely to reach $4.7 billion by 2025.
The most well-known tissue engineering company is the San Diego-based company, Organovo. It has been actively developing a line of human tissues for use in medical research and drug discovery. These include both normal tissues and specially designed disease models. They are also working on the development of specific tissues for use in clinical patient care. In 2014, they announced the successful printing of liver tissue that functioned as a real liver for weeks. A year later, fully functional human kidney tubular tissues had been generated with the company’s 3D bioprinter. Organovo also teamed up with L’Oreal to advance the development of synthetic skin. Moreover, the company’s first bioprinted products are expected to make it to the FDA in 2018.
US-based CELLINK develops both bioprinters and bioprinting materials for providing ready-to-print or use models for researchers and healthcare providers to enable 3D cell culture, personalized medicine, and enhanced therapeutics. The disruptive technology is used to print tissues such as liver, cartilage, skin, and even fully functional cancer tumors that can then be used to develop new cancer treatments.
Another US-based company, drug manufacturer United Therapeutics 3D bioprinted lung tissues. One day, the company says, it plans to use a printer like this one to manufacture human lungs in “unlimited quantities” and overcome the severe shortage of donor organs. However, they predict that it won’t happen for another 12 years.
In Europe, scientists at the Spanish Universidad Carlos III de Madrid in collaboration with the bioengineering firm BioDan Group have presented a prototype for a 3D bioprinter that can create entirely functional human skin. In June 2018, Poietis, a France-based company, along with Prometheus, a division of Skeletal Tissue Engineering at Leuven, Belgium, announced they had entered into a two-year Collaborative Research Agreement to develop tissues for skeletal regeneration.
In situ bioprinting
Don’t worry if you never heard the expression – it is a relatively new one, and it is more science fiction at the moment than the medical tricorder from Star Trek. It means 3D printing tissues directly at the point of injury – no matter whether it’s about bones, tissues or skin. Sometime next decade, doctors may, therefore, be able to scan wounds and spray on layers of cells to very rapidly heal them.
Researchers are already trying to figure out the concept’s feasibility. Dr. Venu G. Varanasi, Assistant Professor of Biomedical Sciences at Texas A&M University (TAMU) undertakes research on in situ 3D printing of bones. He says that their goal is to one day have treatments for bone defects as easily as a dental filling.
Another innovative team of researchers from the University of Toronto has created a 3D printer that’s not only handheld, but it also prints skin tissue. The portable 3D bioprinter, a bit reminiscent of the BioPen for cartilage drawing, deposits even layers of skin to cover and repair deep wounds, and the researchers say that it’s likely the first device of its kind to form and deposit tissue in situ in under two minutes. It is an amazing innovation!
The challenges of bioprinting
The Medical Futurist doesn’t like to ruin optimistic and positive visions for the future, but bioprinting faces severe challenges from the technological, financial and regulatory point of view.
Currently, the most burning issue is the question of regulation – as an up-to-date, comprehensive set of rules for bioprinting has not yet been drafted. That might be very dangerous since the black market for printed organs might thrive the most if regulations are not sufficiently strict and precise. As soon as scaffolds are available and methods are open source, people around the world might be tempted to start printing unregulated and untested biomaterials and sell them to desperate people. While the FDA reaffirmed the agency’s commitment to a “new era of 3D printing of medical products in December 2017, they have not yet introduced their guidance for bioprinting – and we cannot do anything else but urge them to do so as soon as possible.
The costs of bioprinting also constitute significant challenges. For many research institutes and market players, the vast expenses of the technology also build a substantial barrier to development. Affordable prices of bioprinters might also have a positive impact on research and the appearance of smaller companies for specific sub-sections of bioprinting.
Bioprinting is an overly complicated technology, and its many technological, biological challenges, ethical and regulatory issues can already be seen from this brief introduction. It won’t be applied in practice overnight and looking at it from a distance, it’s still pure science fiction. But it’s gonna be a reality to deal with within decades.