Inside the Weird World of 3D Printed Body Parts
Startups in the U.S. are working on printing nipples and bits of liver tissue, while a Russian provocateur claims to have on-demand thyroids
Laura Bosworth wants to 3D print breast nipples on demand. The CEO of the Texas startup TeVido Biodevices is betting on a future in which survivors of breast cancer who have undergone mastectomies will be able to order up new breasts printed from their own living cells.
“Everyone,” she says, “knows a woman who has had breast cancer.” Right now their options are limited. Reconstructed nipples using state-of-the-art plastic surgery techniques, she says, “tend to flatten and fade and don’t last very long.” A living nipple built from the patient’s own fat cells, and reconstructed to the precise specification of the original nipple, could go a long way to ameliorating the psychological trauma often associated with mastectomies.
Bosworth readily acknowledges that significant obstacles must be overcome before 3D printed breast parts become an affordable reality. Despite the waves of hype that surged after Anthony Atala, a Wake Forest professor, wowed a TED crowd in 2011 by purporting to print a human kidney on stage, no one has yet used a 3D printer to create a functional human organ.
The science is only half the battle. Venture capitalists aren’t exactly beating down the doors of TeVido. It’s a lot easier, observes Bosworth, to raise money “for an app that lets you order a taxi” than for a biomedical breakthrough that will cost millions of dollars in R&D before beginning the lengthy process of clinical trials needed to bring a product to market.
Yet Bosworth is convinced that a $6 billion market awaits whoever gets out of the lab first. “The field itself has grown tremendously,” says TeVido co-founder Thomas Boland, one of the first scientists to start modifying ordinary 3D printers to print layers of living cells instead of ink. Researchers far afield, in China and Russia and Switzerland, at Ivy League labs and in the biotech hotbed of San Diego, are all pushing bioprinting forward. The disciplines of material science, cell biology and computer-controlled manufacturing are all merging.
If we believe everything we’ve heard recently, we’ll be 3D printing our food, our cars, our homes, our electronics—heck, the entire structure of globalized trade will be disrupted when we’re 3D printing everything we need in our living rooms rather than having it shipped in containers from China. The possibilities seem near infinite, even if the present-day realities are constrained.
As overblown as this swirling rhetoric may seem, the realms of science fiction and cold, hard bioprinting fact have convened at least once in real life, in the uncanny meeting of the minds of a nipple builder, a pioneer in tissue fabrication and a (possibly) mad Russian futurist. In that brief convergence one can glimpse the grandiose visions that cautious scientists tend to keep to themselves. Absurdity mingles with the commonplace. And you’re reminded of the most astounding thing of all: how today we’re talking, in matter-of-fact, business-savvy tones, about the actual printing of human body parts.
Now, back to the nipples.
In 2000 Thomas Boland was an assistant professor at Clemson University, in South Carolina, when he first conceived of modifying a standard HP inkjet printer to place layers of cells on top of one another, earning him the sobriquet “the grandfather of bioprinting.” He is now the director of the biomedical engineering program at the University of Texas El Paso. In 2010, Bosworth, a retired executive who previously worked at Dell Computers, met Boland through a mentoring program that matched entrepreneurially minded scientists at the university with business veterans.
“The more I learned about the potential for this technology, the more I thought that this was amazing stuff,” recalls Bosworth. “I said to Thomas one day, ‘we should start a company,’ and he said let’s do it.”
It’s easy to understand Bosworth’s fascination. The technology of 3D bioprinting is at once relatively simple to describe and utterly astounding. Instead of extruding multiple layers of plastic or some other composite to create an inanimate physical object, a bioprinter prints a “bio-ink” of living cells. Typically, layers of different cell types are intermixed with layers of an “extracellular matrix”—a gel in which the cells are suspended.
Cell biologists have been culturing cells and attempting to fabricate larger structures for decades. The advantages delivered by 3D printing, says Boland, are in its precision, flexibility and speed. Different types of cells can be placed in specific locations much more quickly than one could achieve by hand. Speed is of the essence, because the slower the process of assembly, the more likely it is that the cells will die. Using multiple printer heads containing solutions of different cell types and gels, extraordinarily complicated structures can be constructed in short periods of time.
Putting cells in position swiftly is only the beginning. Figuring out how to keep them alive is widely acknowledged as the biggest obstacle scientists face in achieving the holy grail of building fully functional organs that can be transplanted into human bodies.
In the organs in your body, cells are kept alive by nutrients delivered by networks of veins and capillaries—its vasculature. The kidney printed out by Anthony Atala at TED, though shaped like a human kidney, did not have this support network. “Embedding the microvasculature into the printed construct,” says Boland, “has proven very difficult.”
No one, at this point, can say with authority when and how the vasculature problem will be solved. At Harvard’s Wyss Institute, for example, a team led by Jennifer Lewis has won widespread attention for a process in which a branching network of tubes gets printed throughout the extracellular matrix using a bio-ink with a very special property — it melts when it cools. After the full tissue construct is printed, complete with living cells and extracellular matrix and a filament of branching tubes, Lewis’ team chilled the whole thing and sucked out the melted bio-ink, leaving behind an empty network of tubes that, theoretically, can be used to funnel nutrients to the cells.
Boland, who now serves as an advisor to TeVido, says his El Paso lab has been experimenting with printing out “channels” of epithelial cells, the cells that line the walls of blood vessels. The goal is to see if the cells can be induced to self-organize into functional structures, although Scott Collins, TeVido’s chief technology officer, citing intellectual property issues, declined to go into much detail.
“In terms of deliverables, have we made organs yet? No,” Boland says. “But we are getting closer.”
Adds Collins: “we aim to be the first.”
The main problem blocking TeVido from getting to the promised land, said Collins, is not the science but the funding. So far it has been scrimping along on various government grants. In January TeVido even took the unprecedented step of running an Indiegogo crowd-funding campaign, in which the company raised the $30,000 it said it needed to file its patents.
The vision of breast reconstruction from living cells is obviously exciting. The reality—the crowd-funding of tens of thousands of dollars to file patents, the long haul from the lab to clinical trial to the human body—is a bit more mundane. It’s a lot harder to build new body parts than it is to code a new app.
But in an era when technological change driven by computer hardware and software wizardry is ubiquitously lauded as instantly disruptive, the distinction between amazing vision and plodding scientific progress sometimes get lost. Indeed, one could argue that over the last few years, the realm of 3D printing technology is where this distinction has gotten most confused.
Last November, a news report in Russia Today sent a shudder of excitement through the cluster of blogs and tech sites that cover bioprinting. Scientists at a Moscow laboratory called 3D Bioprinting Solutions announced that they would be able to print a functioning mouse thyroid gland by March 2015. Even better, declared the director of the lab, Vladimir Mironov, by 2018 the lab would start printing fully transplantable kidneys.
“The one who will be the first to print and then successfully transplant the kidney to the patient—who will stay alive—will for sure get a Nobel prize,” said Mironov.
Mironov was probably not wrong in his prediction that whoever first successfully bioprints a working human kidney will be showered with worldwide acclaim. Never mind the psychological benefits of improved techniques for breast reconstruction; the need for more kidneys is a pressing issue of life and death. In the U.S. alone more than 100,000 people are on the waiting list for a kidney transplant right now—but only 17,000 transplants took place in all of 2013. Successful bioprinting of human kidneys will save thousands of lives.
I don’t normally put huge stock in Russia Today as a reliable news source, but I was very curious. I wanted to know, for example, how Mironov intended to solve the vasculature problem? My efforts to reach him, however, failed.
My efforts to Google him, on the other hand, were highly entertaining.
For starters, in 2011 Mironov wrote an article for The Futurist predicting that we would soon be printing out entire human beings.
It is not difficult to predict that changing the human body will eventually be as routine as changing clothes. Cosmetic surgery will fuse with fashion.
Human-printing technology would eliminate the need to wait 18 years in order to get a fully developed adult: Humans could theoretically be printed on demand and be functionally ready in days or weeks. The brain could be replaced with biochips, though brain research would need to advance to such a level that brains could be reverse engineered and manufactured.
The line “cosmetic surgery will fuse with fashion” contains some nuances that could apply to bioprinted breast nipples. But the notion of bioprinting complete humans on demand in days or weeks? To paraphrase Thomas Boland, such a task seems likely to prove very difficult.
But the plot thickens. In 2003, while employed as a researcher at the Medical University of South Carolina, Mironov was a co-author of a paper that outlined the prospects of using 3D printers to fabricate human tissue. One of other co-authors of that paper was none other than Boland! A third author, Gabor Forgacs, a biophysicist at the University of Missouri, ended up co-founding a company called Organovo that successfully went public and is now bioprinting small samples of human liver tissue for purposes of pharmaceutical drug testing. Mironov’s name is on a patent for engineering tissue that is currently owned by Organovo.
Several years after helping usher in the age of bioprinting with his 2003 paper, Mironov achieved a small measure of pop-cultural notoriety (and an appearance on the Colbert Report) for his work on a PETA-funded project to create in-vitro meat, a.k.a. “schmeat.” Mironov’s goal: nothing less than assuring a sustainable future food source for humanity.
By 2011, Mironov was poised to become director of a $20 million Advanced Tissue Biofabrication laboratory at MUSC. But in February of 2011, he was suddenly suspended and his lab shut down for reasons that remain mysterious, but appear to have involved some serious interpersonal conflicts. A dean at the university said only that Mironov had engaged in “unacceptable behavior.” Mironov told Nature that “my research is blocked. They say I am unstable. It has become surrealistic.”
After 2011 Mironov’s trail becomes more obscure. He appears to have spent some time conducting research in Brazil while authoring visionary articles for the Futurist, before popping up with his new company and laboratory in Moscow.
Let’s review: a one-time PETA-funded synthetic meat researcher who believes that eventually we will be bioprinting complete humans with bio-chipped brains is now hard at work using 3D printers to fabricate mouse thyroid glands in Russia. This is not the plot of the next Thomas Pynchon novel. This is cold hard reality.
And yet, by tracking down the startups co-founded by Mironov’s 2003 co-authors, I ended up learning about TeVido and Organovo, real companies employing real scientists to do real stuff. In the world of bioprinting, the line between science fiction and peer-reviewed research is very, very slender.
Organovo, says Michael Renard, executive vice president of commercial operations, is “far and away the leader” in commercializing the products of bioprinting technology.
Originally founded with the intent of manufacturing bioprinters for sale to others, Organovo eventually decided, after discussions with investors and pharmaceutical companies, that there was a better chance at making and deploying their technology in the drug-testing business, Renard said. In November, Organovo announced the commercial release of 3D printed “Human Liver Tissue for preclinical drug discovery testing.”
The liver tissue samples produced by Organovo are a far cry from fully functional liver organs. They are tiny slices of tissue, three millimeters long and wide and one millimeter tall, and guaranteed to survive for only 40 days. They do not incorporate functional vascular structures. But they do, in theory, solve a serious problem for drug companies—the inability to test drugs on living human tissue without first having to go through a lengthy and expensive FDA approval process.
That may not sound as sexy as printing a kidney or even a nipple, but the long-term implications, if it works, could be significant. The overall process of drug discovery and development could be vastly accelerated by testing drugs on artificially manufactured tissue. The morally questionable process of animal testing could be avoided altogether! And if the business of drug testing generates enough revenue, Organovo might be able to expand its capabilities beyond mere slivers of tissue to more complicated structures.
“We’ve proved the concept, we have reduced it to practice,” Renard said. “The challenge is to continue going through the development process, and building tissues that go beyond liver — kidney, lung, skin.”
Renard declined to comment on Mironov’s claims for imminent bioprinting success in Russia. But there is clearly a connection to trace between the wild claims of the eccentric Schmeat and biochips-for-brains visionary and the more prosaic science being done in El Paso and San Diego.
The very notion that in 2015 we are printing human tissue at all is wild. And maybe, just maybe, the fact that printing organs turns out to be harder than some early evangelists suggested makes the story more interesting, not less. The speed with which software can create new worlds — new apps, games, platforms, 3D printed guns! — sometimes creates the impression that we can work equally lightning-fast magic tricks in the much more complicated and tangled world of biology.
But when one reviews what’s happening in labs all over the world, it seems clear that the merging of material science, digital technologies and cell biology will eventually produce wonders that make all our software tricks look like child’s play. Even if a bioprinted nipple is a decade—or two—away, the disruption that’s coming seems almost impossible to grasp.