3D Printing Is a Matter of Life and Death
By Matt Petronzio
When Kaiba Gionfriddo was born prematurely on Oct. 28, 2011, everything seemed relatively normal. At 35 weeks, his doctors’ main concern was lung development, but Kaiba was breathing just fine. Doctors deemed him healthy enough to send him home within a few days.
Six weeks later, while the Gionfriddo family — parents April and Bryan, and two older siblings — were eating dinner at a restaurant, Kaiba stopped breathing and turned blue. After 10 days in the hospital and another incident, physicians diagnosed the infant with severe tracheobronchomalacia; his windpipe was so weak that his trachea and left bronchus collapsed, preventing crucial airflow from reaching his lungs. So Kaiba underwent a tracheostomy and was put on a ventilator, the typical treatment for his condition.
It didn’t work. Almost daily, Kaiba would stop breathing and his heart would stop. The prognosis wasn’t good. So his doctors tried something revolutionary: a 3D-printed lung splint that could save his life.
Glenn Green, MD, associate professor of pediatric otolaryngology at the University of Michigan, and colleague Scott Hollister, PhD, professor of biomedical engineering and associate professor of surgery, used 3D printing technology to create a bioresorbable device that instantly helped Kaiba breathe. It’s a prime example of how 3D printing is transforming healthcare as we know it.
Green and Hollister had already developed a prototype of the 3D-printed splint, a sort of tubular scaffolding designed to fit around a patient’s airway and inflate his bronchus and trachea. It was nearly ready for testing, but Kaiba needed help immediately. He rested in the intensive care unit with around-the-clock sedation, intermittently paralyzed.
Kaiba’s condition is especially rare. Approximately 1 in 2,200 babies is born with tracheomalacia, in which the tracheal cartilage softens and leads to collapse. Severe cases like Kaiba’s, when both the trachea and bronchus give way, comprise about 10% of that number. It’s an incredibly frightening condition — even a common cold can cause a baby with tracheobronchomalacia to stop breathing.
April Gionfriddo worried the 3D splint wouldn’t work, but it was the only option left to save her son. “At that point, we were desperate,” she tells the University of Michigan Health System.
“Anything that would work and make him live, we would take it and run with it.”
She was even a little intrigued by the novelty of the procedure, saying it was almost like “science fiction.”
3D printing is one of the most popular topics in the tech space now, though it isn’t new. 3D printing can be traced back to the mid-1980s, when Chuck Hull invented and patented stereolithography, and founded 3D Systems, Inc. For the past 30 years, engineers have made strides with the technology, which is now used to produce everything from engineering prototypes to jewelry and housewares.
Yet while 3D printing is changing the way consumers think about mass manufacturing, a parallel revolution is only gradually entering the mainstream consciousness. Behind the scenes, doctors and biomedical engineers are experimenting with the technology, already saving and otherwise improving lives in the process.
So far, 3D printing has helped produce jaw transplants, skull implants, millions of hearing aids and a wide variety of prosthetics — for both humans and other animals. Some scientists have developed 3D printers (“bioprinters”) that print layers of skin tissue, artificial blood cells, miniature human livers and even bionic ears.
Like in Kaiba’s case, doctors once treated many of these instances with traditional solutions. Technicians handcrafted hearing aids and dental appliances from molds; doctors fitted prosthetics to residual limbs; patients received transplants, albeit slowly, from viable donors.
The difference is 3D printing allows for speed, efficiency and customization, three factors that can make a life-altering — hopefully life-saving — difference.
“This is a total game-changer,” Green says. “It’s totally different from how things were before. This is an exciting time to work in medicine.”
The technology behind conventional 3D printing is fairly simple to explain. After a 3D printer reads the design you’ve created with computer software, it passes over a platform, much like an inkjet printer, and deposits the desired material in layers. The process varies according to the model and the size of the object, but a 3D printer typically sprays, squeezes or otherwise transfers a material onto the platform in a matter of hours.
To create Kaiba’s tracheal splint, Green and Hollister obtained emergency clearance from the Food and Drug Administration. The doctors took a CT scan of his trachea and bronchus to produce a precise image, from which they could design the device. Using computer modeling software and making some modifications, they created a splint that perfectly matched Kaiba’s windpipe and printed it with a biodegradable polyester called polycaprolactone.
The splint goes around the outside of the bronchus, then sutures pass through the splint to tether the trachea through the inside. This expands the bronchus and inflates the trachea. With growth, the splint opens up.
Even though Green and Hollister sized the design to Kaiba’s bronchus, they crafted three or four increments of about a half a millimeter above and below the diameter from his scan. Then they made about five copies of each, just to make sure they had enough going into the operating room.
When they implanted the splint on Feb. 9, 2012 at the University of Michigan’s C.S. Mott Children’s Hospital, Green says it established an opening in the bronchus. Kaiba’s lungs immediately started moving. He expects the device to dissolve completely within three years, when Kaiba’s windpipe will have grown in the correct dimensions, big enough that it won’t further collapse.
As a surgeon, Green explains that he can’t match the ability of a computer specifically tailored to a patient’s image.
“There are a bunch of things that I hand-carve or hand-make,” he says. “My abilities are down to around a millimeter, maybe. I can get a microscope out for some small applications, but to do that in the operating room, to go sub-millimeter resolution, is not worthwhile. And I can’t do it with a big case like [Kaiba’s]. It’d be impossible to do.”
More than for precision’s sake, Kaiba’s doctors turned to 3D printing because traditional treatments simply weren’t working. Tracheostomies, ventilation and sedation, while sometimes successful, can pose very serious health problems to children. That’s why Green and Hollister began working on an alternative, even before Kaiba was born.
“Ventilation is actually a very difficult regimen, and they usually have kids on that between one and two years,” Hollister says. “There are severe complications with the ventilation, including recurrent pneumonia, and it’s a very expensive treatment. Over the course of the lifetime of the child, it may cost upwards of $1 million.”
The splint, in this particular case, was inserted at no cost to the Gionfriddos, since it was considered a research project. Green explains, however, that the initial price for such devices in the future will be relatively high, because of expenses associated with purchasing the 3D printer, the sterilization, etc. That said, the raw material is very inexpensive — the polycaprolactone splint costs less than $10, and it can be fashioned in about 24 hours.
“This is one of those things that starts off really expensive, and then the cost gets driven down really quickly. And I think that will happen with personal 3D printers, as well. A regular person can already afford to buy a 3D printer to put on your desk. That’s amazing to me,” Green says.
An iconic painting hangs at the Countway Library at Harvard Medical School. The scene shows a gaggle of physicians crowded around two patients on operating tables — one in the front room, another in the back, almost as if mirroring each other. Men in white lab coats stand outside the doorway on the right, hanging slightly past the frame, talking excitedly while pointing to their notepads. Something important is about to happen.
The painting depicts the first human organ transplant in history — a kidney, in 1954. Anthony Atala, MD, director and chair of Wake Forest Institute for Regenerative Medicine in North Carolina, projected the painting onto a screen before beginning his October 2009 TED Talk.
“We’re still dealing with a lot of the same challenges as many decades ago,” he shares with the audience, referencing the painting. “Certainly many advances, many lives saved. But we have a major shortage of organs.”
“Atala tells Mashable a patient dies every 30 seconds from diseases that could have been treated with tissue regeneration or replacement — a statistic likely to worsen over time with the aging population.”
That’s what he and his colleagues at Wake Forest hope to curb. Wake Forest is one of the largest facilities in the world dedicated to regenerative medicine. Its scientists were the first to engineer lab-grown organs — human bladders — which they successfully implanted into seven patients at Boston Children’s Hospital in 2006.
“The bladders were individually handmade for each patient using biomaterials and the patients’ own cells,” Atala says. “The 3D printer we’ve designed is a way to scale up this process and make it more precise. Because the printer is controlled by a computer, cells can be placed in very exact locations — something that cannot be accomplished by hand.”
The biomaterials Atala refers to are essentially materials compatible with the body. They can be natural (like collagen), synthetic or a combination of the two. Biomedical engineers can weave biomaterials together, or they can print them, similar to how Kaiba’s doctors manufactured his splint.
As a result of this bioprinting technology, and keeping in mind that 90% of people on the transplant list are waiting for a kidney, scientists at the Wake Forest Institute 3D-printed a kidney in seven hours, using biomaterial and human cells.
Bioprinting is similar to conventional 3D printing in that it’s a combination of related technologies used to print out living structures, and each one has its own process, limitations and potential achievements.
Autodesk, one of the leaders in computer-aided design software since it was founded in 1982, has worked to push innovation in 3D bioprinting for the past three years. Essentially, the company is trying to look at life as a design space.
“One of the things that makes bioprinting different from conventional printing is that the design software has to understand biology as well as the mechanical aspects of the designs,” explains Carlo Quinonez, principal research scientist for Autodesk’s Bio/Nano/Programmable Matter Group. “With CAD software for a conventionally 3D-printed object, you specify the design, you specify geometry — angles, distances and things like that. With bioprinting, the CAD software has to understand the biochemistry of it, too — things such as metabolism and nutrient diffusion.”
While this sounds like a tall order, Quinonez says that getting CAD software to understand biochemistry is actually something he and his team have a handle on. What’s really complicated is getting the software to understand what will happen to a living structure after it’s printed.
“If we have a bioprinted part going directly into a person, it’s going to need to [be conditioned] for some period of time before it becomes usable. The cells need a little time to recover from the printing process,” he says.
Even over a period of a day or two, the structures can change — cells “settle,” or begin to form bonds. Autodesk is working to simulate and predict how bioprinted structures will grow and change over time, but that’s something the science community is helping them with. The team collaborates with various researchers, scientists and companies, such as Organovo, which is currently building a number of 3D tissue models for research, drug discovery applications, surgical therapy and transplantation.
To the average person, regenerative medicine and 3D printing in healthcare still seem largely experimental. Atala says this is changing, but it will take time.
“Regenerative medicine therapies are currently available to small groups of patients through clinical trials, which [can] lead to widespread approval,” he says. “To ensure patient safety, we must be cautious and take things one step at a time, but I do believe that in the future patients will routinely be offered regenerative medicine therapies.”
Today, the team at the Wake Forest Institute works to engineer replacement tissues and organs, and to develop cell therapies for more than 30 different areas of the body. It’s currently developing a specialized 3D printer as part of the Armed Forces Institute of Regenerative Medicine, a federally funded initiative to apply regenerative medicine to battlefield injuries. In other words, this printer may be able to print skin grafts directly onto patients’ wounds.
In February 2014, key patents that currently prevent competition in the market for the most advanced and functional 3D printers will expire, according to Duann Scott, design evangelist at 3D printing company Shapeways.
For Autodesk, as Carlos Olguin, head of the Bio/Nano/Programmable Matter Group, explains, it’s less about patents and more about “democratizing the space in a responsible way.”
“There’s currently no standard software for 3D bioprinting, and therefore, no practical way for the community to exchange designs.”
“Our efforts focus mostly around how can we scale very complex practices that require, to be truly effective, a scientist coupled with a computer scientist to be able to create value in 3D bioprinting,” says Olguin. “Our goals are much bigger than the immediate intention to try to monetize or to try to do some kind of revenue opportunity in the immediate future.”
Now, Autodesk is developing Project Cyborg, a platform to enable researchers and scientists to develop computational models and receive information in a more open and accessible way.
Despite no standard way to create and share designs, 3D printing is filling the holes left behind by traditional medicine.
“I think that shortages in organ donors aren’t going to be alleviated anytime in the near future,” Olguin says. “I think there’s going to be an increased need for having replacement organs available, and bioprinting is currently the only solution on the horizon for making new adult-sized organs. There’s just no other way to do it.”
For adults and children like Kaiba who have no alternatives, Green and Hollister believe 3D printing will soon become the norm for specific treatments matching a patient’s defect.
“Kaiba’s was really the first case in which we used a device when there was no other option, and he would have died otherwise,” Hollister says. “Custom applications are the wheelhouse for 3D printing, because you can take a patient’s scan, you can design a device specifically for that patient and you can then build multiple copies of it. I think you’ll see more dissolvable devices printed for medical use and surgical reconstruction.”
Kaiba was taken off ventilator support 21 days following the splint procedure, and he hasn’t had any trouble breathing since then. He still has regular and relatively close follow-up appointments at the University of Michigan. He uses a valve to talk. He’s mildly delayed in physical development, which Green says is unsurprising, considering how long Kaiba was paralyzed.
But Kaiba still looks and acts like a normal kid, playing with his brother and sister and hanging out with the family dog, Bandit. He even gets himself into trouble, scooting across the floor and “getting into everything,” according to his mom.
It was 3D printing technology that allowed Kaiba to become such a happily curious and healthy child, and perhaps many other children can benefit from the same innovative treatment in the future. 3D printing is more than the tchotchke on your desk — it is saving lives.