Can 3D printing solve the shortage of transplant organs?

Release date: 2017-08-02

3D printed silicone heart created by ETH Zurich engineers

On July 31st, the Guardian website wrote that we are far from 3D bioprinting human organs? Can the technology solve the shortage of transplant organs? Scientists are working hard to make alternative human organs using 3D printers. However, although the possibilities of the technology are exciting, there are now concerns that it will allow humans to "play the role of God."

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Erik Gatenholm first saw the 3D bioprinter in early 2015. At that time, his father, Paul, a professor of chemical and biopolymer technology at Chalmers University of Technology in Gothenburg, bought one for his family. Its price is around $200,000. "My father said, 'This thing can print human organs.'" Kato Holm recalls, and now he still feels amazed. "I said, 'Nonsense!', it printed a small cartilage. It's not cartilage, but it looks like it might be cartilage. At that moment, I think, 'This is so cool! '"

Kato Holm, who had an ordinary 3D printer very early, was thinking about what he wanted to do in the 3D bioprinting field. His accent may be a bit strange - he grew up in Sweden and the United States, his father is a visiting professor in the United States - but his goals and ambitions are well thought out. Kato Holm founded his first biotech company at the age of 18, when he realized that if the machine had the potential to print organs, as his father said, it had the potential to revolutionize medical care. industry.

Organs used for life-saving transplants are in short supply around the world. For example, in the UK, if you are going to have a kidney transplant now, you have to wait an average of 944 days through the National Health Service (NHS). The liver, lungs and other organs are also in short supply. The lack of transplanted tissue is estimated to be the number one cause of death in the United States. In the United States, approximately 900,000 deaths each year, or one-third of deaths, can be avoided or delayed through the transplantation of organs or engineered organizations. It is conceivable that the demand for transplanted organs is extremely large.

Bio-ink

Can 3D printing solve the shortage of transplant organs?

Eric Katoholm and Hector Martinez, two co-founders of Cellink

Kato Holm’s father introduced Héctor Martínez, a student who is pursuing a doctorate in organizational engineering, and Ivan Tournier, another student who also participated in the group discussion. He knows. "We were discussing some experiments at the time," said Kato Holm, 27.

"So I told them, 'Why don't we buy the printing ink we need online?' Ivan said, 'Without ink, you can't buy it.' I said, 'What do you mean?' This is what I heard. The most stupid thing. There are a lot of printers on the market, and you can buy ink. He said, 'No, you don't understand what I mean, you can't buy ink. You have to make it yourself, you have to mix in something.' Then I said, 'Let's make ink yourself!'"

Cellink was born in January 2016 when this inspiration suddenly flashed. Although the technology is something in science fiction, its business philosophy is similar to the classic "razor and blade." In this long-established model, you are actually giving away the razor and then making money through the interchangeable blade. The same is true for inkjet printers: Everyone knows that the real money-making is the replacement of ink cartridges.

In the field of bioprinting, Kato Holm and Martinez developed the world's first standardized bioink and marketed it: it is made primarily from a material called nanocellulose alginate. The material is partially extracted from seaweed. If you have a 3D bioprinter, that ink is a ready-made product that you can buy directly.

Cellink's influence is remarkable, especially considering that it was born soon. The company has won a series of awards for innovation and entrepreneurship, and is also funded by the Swedish version of the Dragons' Den reality show. Just 10 months after its establishment, Kato Holm entered the stock market and was listed on the NASDAQ First North market. The over-subscription ratio of its IPO (IPO) reached a staggering 1070%.

When I met with Kato Holm in Gothenburg, he seemed to be thinking about how to use the company's new funding. Cellink's office was in chaos: there was a piece of iron on the floor, and a suit jacket was hung on it, making it easy for him to attend a scheduled customer meeting. He and Martinez, 32, usually work 16 hours a day. "The sofa is very comfortable to lie down." Kato Holm laughed. His office actually didn't have a place to sit down. Cellink's team of people is expanding too fast, and both Kato Holm and Martinez have to give their seats to new hires. "We are donating them to science." Kato Holm said with a smile.

But Kato Holm is very clear that this is the era of bioprinting. “As an entrepreneur, you always have to look for the blue ocean.” He said, “Entrepreneurs always ask, 'Where is there a new field that makes you synonymous with it? Can you occupy it?' I think, Bio-ink and bio-printing are such new areas."

He shook his head in disbelief. "Nobody actually made bio-ink before!"

What Kato Holm is happy to admit is that bioprinting is a surreal concept and a concept that raises some ethical concerns. It works much like a common 3D print: you first use a computer program to make a virtual form of what you want to make, and then let the printer print it into a finished product bit by bit. But unlike ordinary 3D printers that can only print inanimate objects such as jewelry, figurines, car parts, etc., bio-printers offer the possibility of creating living tissue.

In the beginning, this may mean printing skin or cartilage, which are relatively simple structures that are simpler to grow in vitro. However, the pioneers of the technology believe that in the end they will be able to build complex organs from scratch, such as the heart and liver. These organs may be applied to human transplants by then.

Research around the world

Scientists and commercial companies around the world are involved in such projects. In fact, some kind of competition has started. Organovo in San Diego has been in the field since 2007 and has achieved some success in printing liver, kidney and heart muscles. In 2015, it announced a partnership with cosmetics giant L'Oréal to provide 3D printed skin. Their ultimate goal is to eliminate the need for animal testing.

L'Oreal is investing a lot of resources in developing bioprinting projects. In September last year, the company revealed that its scientists are also working with the French startup Poietis. The goal this time is to create synthetic hair follicles. The project is actually extremely complex: there are more than 15 different types of cells per hair follicle, involving a cycle of fiber production that requires catalytic stimulation in a test tube.

Many people have tried this aspect and finally failed. But L'Oreal and Poietis believe they are close to overcoming the project. The key is the bioprinter developed by Poietis: most machines use a nozzle to squeeze out bio-ink; their machines use a laser that stores cells one by one, dropping 10,000 drops per second without damaging the cells. “It works in a very simple way, similar to inkjet printing,” explains Fabien Guillemot, CEO and chief scientific officer of Poietis, in a video that announced the collaboration, “through continuous Layered cell droplets are layered on a surface that prints a 3D structure, in this case a biological tissue is printed."

Poietis calls its innovative technology 4D bioprinting. “The fourth dimension is time,” said Gillesmoort. “Because our laser-assisted bioprinting technology can basically print one cell at a time, it allows us to direct the interaction between cells and their environment until they form the biological function we want.”

In the short to medium term, L'Oreal hopes that its sunscreen and anti-aging serum will become more effective as it is now able to continuously test products in a material that reacts like human skin. Maybe, your hair will become more shiny and beautiful after using its shampoo in the future. But it is obvious that the impact of such technologies may be far from being limited to cosmetic areas in supermarkets.

If the skin can be printed in the lab, it is not difficult to imagine that it will be used to treat severely burned skin. At present, skin graft surgery is the most common treatment for skin burns, but it can cause bleeding and infection, and recovery time is usually very long.

At the same time, the development of synthetic hair follicles seems to lay the foundation for commercial products or transplants that reduce hair loss. “Obviously, our future goal is to be able to test innovative molecules using the hair follicle system created in test tubes,” said José Cotovio of L'Oréal's Research and Innovation department, “and to enhance our hair aging. Understanding of the key processes behind the phenomenon of hair loss, hair growth and so on."

Ethical concerns

This is just the tip of the iceberg – other researchers are exploring how to make human organs. "Biological printing has great benefits for humans," Kato Holm said. "You will die because your organs will get worse. This is why you die. If we can start replacing organs in the body, then We may be able to extend our life... that's so cool!"

We are a little bit closer to making these R&Ds a reality. But the difference is not very far: Kato Holm believes that bio-printing skin may still be available in five years. "In 10 years, we will begin to see some cases of cartilage implants, whether it is partial cartilage or the entire cartilage implant." He said, "Orplant replacement can be achieved in our lifetime." He added with a smile: "In Our lifetime can be achieved."

Inevitably, bioprinting has raised some ethical concerns. They include: worrying about the quality and effectiveness of artificial skin and implants, and accusing bioprinting will allow humans to "play the role of God." Perhaps the most comprehensive survey of these issues is a survey conducted by the team at the Department of Technology and Innovation Studies at the University of Edinburgh.

The research team led by two doctors, Niki Vermeulen and Gill Haddow, doesn’t feel the horror of science fiction like monsters in Frankenstein’s creatures. Worried. "If God exists and God can create and influence life, there are already many technologies that allow humans to play the role of God, such as genetics." Haddo said, "Bioprinting allows people to make small organs. Organized for medical applications."

Cost problem

They believe that one of the bigger obstacles that 3D bioprinting technology needs to overcome is cost. It is easy to expect that the ability to make artificial organs will solve the problem of long list of organ transplant waiters, but that is unlikely to happen. “This is an extremely expensive technology. If it can be achieved, only a small number of people will be able to bear the cost.” Vermelan warned that “the current health inequalities and differences in health care treatments everywhere may be It will also make many people use the technology."

They concluded that the problems and surgical delays faced by patients in the UK's national health care system, the US health care system, and other places that require organ transplants will "continue in the era of bioprinting."

“You might think that exporting a relatively cheap bio-printer to a country where the health care system is imperfect can give people access to treatments like this. But in fact, these printers can only be used to have the ability Take advantage of their healthcare infrastructure."

Can 3D printing solve the shortage of transplant organs?

RegenHU 3D bioprinter in operation at Zurich University of Applied Sciences

Cost is undoubtedly the roadblock for the early development of 3D bio-printing. EnvisionTEC's 3D Bioplotter, RegenHU's ​​3DDiscovery and other best machines are priced at more than £150,000, so they are usually only seen in college laboratories. However, Cellink is also eager to change this situation. Although it started with the supply of bio-ink, it did not take long to enter the hardware market. Kato Holm’s office is home to “Bob,” a nickname for the Inkredible+3D bioprinter developed by Cellink, which he often brings to trade shows.

Can 3D printing solve the shortage of transplant organs?

Cellink's 3D bio-printer is smaller than the small refrigerator in the hotel room

Inkredible+ is an attractive machine: a small refrigerator that is slightly smaller than the hotel room, clean, white design with blue LED lights. But what really catches the eye is its price. Cellink has created three 3D bioprinters ranging in price from £7,600 to £29,900. Kato Holm explained that they were able to save on manufacturing costs, in part because they used cost-effective 3D printer components instead of ultra-expensive motor rail systems. In addition, this is in line with the "razor and blade" business model: Cellink knows that the more people who have a 3D bio-printer, the more bio-ink it sells.

Kato Holm is proud that his company is driving down the cost of 3D bioprinting. Cellink's clients include MIT, Harvard University, University College London and other leading universities, and it also offers this technology to amateurs. Kato Holm doesn't know how these people will use their machines and inks—perhaps to print tissue to test drugs, or to extract cells from cancerous tumors, and then research to find the best treatment through various attempts. - But this is where the new technology is exciting.

“Because of our products, many large biotech companies feel very uncomfortable,” said Kato Holm. “But to be honest, consumers are the people who drive the market, consumers want to get our products. Saying, I don't know where the cure for cancer will be born. I don't know if it will be born in India, Japan, South America or New York, but we want to give everyone the opportunity to study treatment."

Print the human heart challenge

Why do we want to print a heart?

In addition to geometry, the heart is one of the least complex organs in the human body. It does not perform complex biochemical reactions like the liver and kidneys. Its principle of operation has been understood by scientists, unlike other organs such as the brain. Based on this, the heart may theoretically be one of the easiest organs for bioprinting, so it is very suitable for the bioprinting industry to start with it. In Europe, 3,500 people are waiting for a heart transplant, many of whom have needed a new heart for more than two years.

How to bio print the heart?

Perhaps the most promising method is the biologically printed cell scaffold. Bio-printers are first used to print biodegradable cardiac scaffold structures (equivalent to the skeleton of a cell), rather than layering layers of living cells to form a 3D structure like a 3D printer that prints plastic or metal. This scaffold mimics the extracellular matrix of the heart, which provides structural support to the cells and helps guide them to where they should be. The heart cells are then printed into the scaffold where they interact and link to form the structure of the heart. After the cells fuse into the entire structure of the heart, the scaffold can be disassembled, leaving a full-function heart that can be used for transplantation. This technology does exist already, although the scope of application is still relatively small. A stent has been used to bioprint a small piece of working myocardium, which has been shown to repair the heart of a mouse that has been damaged by a heart attack.

Why can't we bioprint out the heart?

Bioprinting a small piece of muscle and biology prints the entire heart is completely different. But why is this happening? Creating a complete organ has a problem to solve: blood vessels. All blood vessels have proven to be difficult to manufacture by bioprinting techniques, and it is impossible to make capillaries smaller in diameter than the smallest cells. Making a viable vascular system would be a remarkable achievement, and NASA would even offer a $500,000 bonus to the first research team that could do it. Its vascular tissue challenge will award a prize to a manufacturer of 1 cm thick body tissue with a full-function blood system that survives in a test tube for 30 days.

How far are we from biological printing of human organs?

When will organ bioprinting become feasible? The industry's forecasts are different, and one team claims that they will be able to print out the heart within six years. No one knows that these technologies will be certified as the exact time to be safe for human transplants. However, given that there are not a few research scientists currently working in the 3D bio-printing industry, and the industry that is expected to exceed $1.3 billion by 2021 has made considerable progress, it is certain that it is not far away from us.

Source: NetEase Technology Report

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