3D printed dinosaur with a flexible body

Printing organs: how ears, skin and noses are made with a 3D printer

• Natalka Pisnya
• BBC Russian Service, USA

March 23, 2018

: she will help you understand the events.

Image copyright, Masela family archive

Luc Masela with his parents one month after the artificial bladder transplant. year 2001.

Now 27, Luc Masela is an athlete with a degree in economics, works for a large exhibition company, travels a lot and recently met, in his words, "the most beautiful girl in the world. " Both she and most of his current friends were extremely surprised when they learned that 17 years ago he survived a dozen and a half operations.

Luke was born with spina bifida - and although he was able to walk, his bladder was severely damaged. By the age of 10, he almost did not leave hospitals: due to improper functioning of the bladder, fluid began to return to the boy's kidneys, doctors diagnosed an irreversible pathology of the organ.

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3D printed organs are here intestinal segment. This would guarantee Luke several years of medically supervised life and a high risk of developing cancer.

The urologist who was taking care of the boy invited the Masela family to take part in an experimental program: to grow a new bladder from his own cells. Then, in 2001, it sounded like science fiction: only nine people took part in the program before Luke. Despite this, his family agreed.

"The essence of the operation was reduced to two stages: first, a piece of bladder tissue was taken from me and, over the next two months, cells were grown in the laboratory in order to grow a new healthy bladder from them," says Luke.

Photo copyright, Masela family archive

Luc Masela, 17 years after the artificial bladder transplant

Next was the transplant operation, which, according to him, lasted 16 hours. “I opened my eyes and saw a cut through my entire stomach, tubes of all possible sizes were sticking out of me, except for them - four IVs and a bottle-feeding machine,” he recalls. “I stayed in the hospital for another month, I was prescribed bed rest, after that I stayed at home for another month.

The operation was performed by Dr. Anthony Atala, Pediatric Regenerative Surgeon. In two months, out of a hundred patient cells, scientists created one and a half billion. Further, an engineering structure was created on a collagen frame: the bladder was “sculpted” like a two-layer pie, the core of which dissolved over time, and it started working like an ordinary organ, taking root thanks to Luke’s own cells.

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Luke and Dr. Atala haven't seen each other for 10 years after leaving the hospital. Once a dying child became the champion of the school wrestling team and went to college.

The professor took charge of the Wake Forest Institute of Regenerative Medicine in North Carolina in those 10 years, but he never forgot about Luke: his bladder was one of the most challenging and most successful projects in his early practice.

By 2018, Atala won the Christopher Columbus Prize for "work on a discovery that will have a significant impact on society"; The Times and Scientific American magazines at various times named him "Physician of the Year", he was also recognized as "one of the 50 scientists on the planet who in the next 10 years will change the way we live and work. "

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In the mid-2000s, Atala's team turned their attention to an ordinary household 3D printer and wrote special software for it; later, specialized machines were created for the laboratory. Now the laboratory "grows" up to 30 different types of cells and organs, as well as cartilage and bones.

One of the team's latest achievements is ears and noses grown outside the human body.

The main customer and sponsor of Atala's developments is the US Department of Defense, and many of the patients are military victims of military operations.

It works like this: first, a CT scan of the ear or nose is done. One of Atala's assistants, Joshua Corpus, jokes that at this stage, people often ask to "improve" the shape of the nose if they thought theirs was too wide or hooked, and the ears if they were too wide.

After that, a special computer code is written, and the printing of the basis of the organs begins.

For this, a bioabsorbable polymer, polycaprolactam, is used. At the same time flexible and durable, in the human body it disintegrates within four years.

After printing, the layers of polycaprolactam resemble lace; after transplantation, their place will be taken by a person's own cartilage tissue in a few years after transplantation.

Polycaprolactam is then saturated with a gel created from the patient's cells, cooled to -18 degrees Celsius - so the cells, according to scientists, are not damaged, they are "alive and happy."

Printing a test kidney sample on a bioprinter

In order for the polymer and gel structure to take shape and become something more durable, ultraviolet light is used in the laboratory - it does not damage cells.

The future implant is printed for 4-5 hours, then it is finally formed and inserted under the epidermis.

Skin can also be grown: children affected by fires were the first to take part in the early trials of Atala - after the "printing" of the skin, scientists observed the patients for several more years. The new skin did not crack, did not burst, and grew with the children.

The most difficult job, according to the scientist, is facial wounds: it is not enough just to stretch the skin, you need to accurately calculate the geometry, align the swelling, the structure of the bones, and understand how a person will look after that.

In addition to the skin and ears, Atala can "print" the bones of the jaws, grow blood vessels and cells of some organs - the liver, kidneys, lungs.

This technology is especially appreciated by oncologists: on the basis of patient cells, it is possible to recreate the body's response to various types of chemotherapy and observe the reaction to a particular type of treatment in the laboratory, and not on a living person.

But the liver, kidneys, lungs and heart are still being tested. Atala says he raised them in miniature, but creating organs from various tissues to real size requires a lot of additional research.

But, according to him, cells were grown in the laboratory and a vagina was created for a girl who was born several years ago with a congenital deformity of the genital organs - several years have passed since the transplant.

Bioprinted polycaprolactam ear implant base

Atala smiles and adds that his team is also working on a working penis. This research has been going on for several years, and the most troublesome for scientists is the complex structure of tissues and the specific sensitivity of the organ itself.

Among others, Igor Vasyutin, a Russian post-graduate student of the First Moscow State Medical University (MSMU) named after Sechenov, is working on this under laboratory conditions. He is a cell biologist, Atala's right hand.

Vasyutin has been in the USA for about a year - he came on an exchange. He is ready to talk about the behavior of stem cells for hours, but becomes less verbose when it comes to Russian science.

At Vasyutin's alma mater, mass regeneration of human organs has not yet been reached and so far they are training on animals: local scientists have "printed" a mouse thyroid gland on a 3D printer.

Research on human organs, however, is also being done there. According to the head of the Institute of Regenerative Medicine at MSMU Denis Butnar, several years ago the Institute recreated a special engineering design of the buccal mucosa. She functioned perfectly for the first six months, but subsequently had to undergo a second operation.

Test specimen of an ear implant exposed to ultraviolet light

In Russia, however, over the past few years, the Italian surgeon-transplantologist Paolo Macchiarini has been practicing in Russia - the man who was the first in history to perform a synthetic organ transplantation operation - a plastic tube that replaced the patient trachea.

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However, seven of his nine patients died, and the breathing tubes implanted in the remaining two subsequently had to be replaced with donor ones.

Several criminal cases were brought against him, including on charges of pressure on patients and fraud, and the world's leading doctors called Macchiarini's operations "ethical Chernobyl."

Will printed organs replace donors?

At the zenith of his career, Macchiarini argued that a new perspective is opening up for humanity: you can "print" any human organ on a printer, create an engineering structure from it, enriched with the patient's stem cells, and get the perfect prosthesis.

Be that as it may, complex human organs - the liver, kidneys, heart, lungs - have not yet been able to grow any regenerative surgeon.

Bioprinting of the so-called simple organs, however, is already available in the US, Sweden, Spain and Israel - at the level of clinical trials and special programs.

The American government is actively investing in such programs - in addition to Wake Forest, cooperating with the Pentagon, the Massachusetts Institute of Technology also receives significant amounts to recreate the work of the liver, heart and lungs.

Skin application test on a burnt wound

According to Professor Jorge Raquela, a gastroenterologist at the Mayo Clinic Research Center, "Bioprinting is one of the most exciting branches of modern medicine, it has huge potential, and the tipping point of the most important discoveries is already close."

Meanwhile, Pete Basillier, head of R&D at analytics firm Gartner, insists technology is advancing much faster than understanding the implications of 3D printing.

Such developments, according to Basilière, even created with the best of intentions, give rise to a set of questions: what will happen when "improved" organs are created, the basis of which will not only be human cells - will they have "superpowers"? Will a regulatory body be created to monitor their production? Who will check the quality of these organs?

More than 150,000 Americans are on the waiting list for organ transplants each year, according to a report from the US National Library of Medicine. Donor organs will receive only 18% of them; every day in the United States, without waiting for a transplant, 25 people die. Organ transplants and subsequent rehabilitation cost insurance companies and patients $300 billion in 2012 alone.

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Most Americans are potential donors: upon obtaining a driver's license, they voluntarily answer the question of whether they agree to donate their organs in the event of a car accident or other dangerous incident . In case of consent, a small "heart" and the word "donor" appear in the corner of the document.

Professor Atala's driver's license is like that - despite all his achievements and faith in the "publishing organs", he is ready to share his with others.

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