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Clinicians Embrace 3D Printers to Solve Unique Clinical Challenges
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For a young child with epilepsy, the daily chore of taking pills can be difficult, but the US Food and Drug Administration’s (FDA’s) August approval of a 3D-printed quick-dissolving version of levetiracetam may ease that burden.
Joe Vela/Shriners Hospitals for Children – Houston
The approval is the latest evidence that 3D printing is taking off in medicine as a way to overcome patient-specific challenges (Voelker R. JAMA. 2015:314[11]:1108). In addition to manufacturers, clinicians themselves are increasingly collaborating with designers and engineers to use 3D printers to tackle unique clinical challenges. The printers, which have become common at major medical centers, are being used to print 3D models of patient anatomy that can be used to practice difficult surgical cases (Michalski MH and Ross JS. JAMA. 2014;312[21]:2213-2214).
Some pioneering centers are using the printers to create lifesaving implantable devices. As clinicians experiment with 3D printers in practice, engineers at laboratories across the country are working to adapt 3D printers to one day produce soft tissues on demand.
One of the first medical applications of 3D printing technology to become widespread in clinical practice has been prosthetics. Gloria Gogola, MD, pediatric hand and upper limb surgeon at Shriners Hospitals for Children in Houston, explained that 3D-printed prosthetics allow patient-level customization. This feature of 3D printing is likely a driving factor behind wider use of the technology in medicine.
Learning to ride a bike is a big deal for every kid, but for kids missing all or part of a hand it can be a special challenge. Experts are working to make it easier by creating inexpensive, durable 3D-printed plastic prosthetics.
One project, led by a nonprofit organization called e-NABLE (http://enablingthefuture.org/), is working to match volunteer designers, engineers, and 3D printers with children in need of a prosthetic. Designs are customized to each child’s needs, Gogola explained. She and other physicians, orthotists, and therapists collaborate with the program to contribute clinical expertise and anatomic knowledge to the design process.
Gogola said most prostheses made for children are expensive and have very basic functionality, so many children missing all or part of a hand go without prosthetics by choice or necessity. Hands children power by moving their arm or wrist cost $4000 to $6000, and electronic hands can run $10 000 to $15 000, Gogola said. And a rapidly growing child might outgrow a device in as little as 6 months.
“When you think about kids, low tech is best,” Gogola said. “Something simple, something rugged, something that it is okay if they break it or outgrow it.”
Children are very dexterous and open-minded so they can often learn to accomplish most daily tasks without a prosthetic, Gogola said. But they may want a prosthetic to hold a water bottle while they screw off the cap, swing a baseball bat, or hold handlebars, she explained.
That’s where e-NABLE comes in. Jon Schull, PhD, a research scientist at the Rochester Institute of Technology in Rochester, New York, launched the organization in 2013 to help meet the global demand for affordable prostheses. Now, a community of volunteer designers and engineers around the world contribute their time to help design custom 3D-printed hands. So far, about 1500 prosthetics have been created through the organization, and many more have likely been created using the organization’s designs. Every design created by the volunteers is made freely available online. This allows anyone with a printer to use an existing design on his or her own, or they can go through e-NABLE’s matching process to have a custom prosthetic designed or an existing design tweaked.
Jordan Miller, PhD, an assistant professor of bioengineering at Rice University, who runs a laboratory studying ways to 3D print living tissues, and his colleagues volunteered their 3D printing expertise to e-NABLE. Gogola approached them last year to help her patients locally.
Now, Miller and his colleagues help design hands for about 5 of Gogola’s patients each month. The materials cost the patient about $50 to $100. Parents typically print out the parts either at a university or library with a printer and assemble them, Gogola said.
“It’s very, very inexpensive,” Gogola said. “If you break off a finger, nobody gets upset, you just print off a new one. If you grow out of it 6 months later, you just print out a new one.”
The prosthetics can also be jazzed up to look like the hand of the child’s favorite super hero or princess. Looking trendy is just as critical as being functional, explained Gogola.
“Hands are out there; people see them,” Gogola explained. For a child who was either born missing part of a hand or lost part of a hand in an accident, it’s nice “to look different in a cool way: a way that everybody wants to see and check out and wishes they had, instead of a way that makes you want to hide your hand,” she said.
Parents and patients are involved throughout the process. Gogola and Miller are currently collecting data on 20 patients using e-NABLE hands to assess their effect on functional outcomes, as well as patients’ views on when the hands are useful and when they are not. Miller and his colleagues teach children and parents how to assemble the hands themselves. Some parents have modified e-NABLE designs on their own. For example, one dad designed a hand with 2 thumbs because his son wanted to hold a toy sword, Miller said.
“It’s really about teaching and empowering people,” Miller said.
The 3D printers also can be handy when physicians need to improvise solutions to challenging cases. For example, Glenn Green, MD, and his colleagues at the University of Michigan’s C. S. Mott Children’s Hospital worked with engineers to create 3D-printed splints to hold open the airways of infants with tracheobronchomalacia. The condition causes frequent trachea collapse, impairing breathing and even leading to death in severe cases.
“We wanted something that would expand as the child grew and that would eventually dissolve,” Green explained.
The team designed customized splints that partially wrap around the airway using imaging of each child’s trachea and computer design software (Morrison RJ et al. Sci Transl Med. 2015;7[285]:285ra64). The splint was then manufactured using a 3D printer and flexible polyester safe for implantation that is gradually absorbed by the body over the course of 2 to 3 years. Children with tracheobronchomalacia typically outgrow the condition as their tracheas grow and become stiffer.
The FDA granted emergency clearance for Green and his colleagues to implant the experimental devices. So far, Green and his colleagues have implanted 5 children with 3D-printed tracheal splints with promising results. The first child to receive a tracheal splint is now an active 3-year-old, with partially dissolved implant and no signs of adverse events (Zopf DA et al. N Engl J Med. 2013;368:2043-2045).
Green and his colleagues are working with the FDA to launch a clinical trial soon as a step toward gaining FDA approval. Already, the FDA has approved 3D-printed skull and spinal implants (http://bit.ly/1mcVxt5; http://bit.ly/1ms1N0e).
While implantable 3D-printed medical devices are still quite rare, Green said that 3D printing facilities are becoming more common at major hospitals. Surgeons in many specialties use 3D-printed models of patient anatomy to prepare for complicated surgeries (Malik HH. J Surg Res. 2015;199[2]:512-522). Green said the use of 3D-printed models in surgery has been “transformative” for the field, enabling residents to gain hands-on experience even before their first patient. The printers also aid clinical decision making. Recently, Green and his colleagues used a 3D-printed model of a fetus to determine whether emergency surgery would be required at birth (VanKoevering KK et al. Pediatrics. 2015;136[5]:e1382-1385).
The fetus had a mass on his face that might obstruct breathing. Normally, Green and his colleagues would opt to deliver the child via cesarean section with the mother under full anesthesia. Then, they would perform an emergency tracheostomy on the fetus while it was still attached to the placenta.
However, that procedure carries risks for both mother and child. So Green and his colleagues used imaging data to create a 3D-printed model of the fetus’ head. The model made it clear that the airway was not obstructed, and the child was delivered through a normal cesarean section. The child has since had surgery to repair what turned out to be protuberant cleft lip and palate.
Eventually, Green and his colleague hope to help other physicians interested in using 3D-printed models or devices for their patients.
“We want to make it so any physician can make a scan and we can make devices,” he said.
Current applications for 3D printers in medicine leverage what the machines were originally designed to do—custom build 3D structures out of stiff materials by assembling them layer-by-layer. But a cadre of researchers around the country is working to adapt the devices to recreate living tissues and organs for research or eventually for regenerating tissues or organs in patients.
A culture of sharing designs for building 3D printers has enabled rapid advances in the field by making them easier and cheaper for laboratories to access. Biomedical engineer Adam Feinberg, PhD, an associate professor at Carnegie Mellon University in Pittsburgh, and his colleagues began building bioprinters based on open-source designs he found on online (http://reprap.org/). Now, Feinberg makes his team’s printer designs and modifications available for others.
“We want to accelerate the pace of innovation,” Feinberg said.
This culture of sharing has helped make bioprinting more affordable. Feinberg explained that a year ago the cheapest commercially available bioprinter cost $100 000, but now the devices sell for $5000 to $10 000. However, laboratories can build their own using Feinberg’s designs for less than $1000.
Sharing printer designs also has allowed researchers to focus more time on the bioengineering challenges of working with living cells. For example, bioprinters may print with hydrogels, which include collagen and fibrin and have a Jello-like consistency. These soft materials can collapse and lose shape during the printing process. But Feinberg and his colleagues overcame this barrier by printing these soft materials within a mold of gelatin microparticles (Hinton TJ et al. Sci Adv. 2015;1[9]:e1500758). When raised to body temperature, the gelatin mold melts, leaving behind the printed tissue that once complete is structurally sound enough to hold shape at this temperature.
While the technology is advancing very quickly, Miller, who also builds his own bioprinters, noted that organs are far more complex than anything currently manufactured and there is still much to learn about the biology and how organs work.
“Human organs have billions of cells,” he explained. That many cells would likely be needed for something like a total liver replacement. But the most sophisticated tissue engineering projects still have millions of cells, he said. Progress also depends on other rapidly developing disciplines, for example, stem cell research that provides the raw materials for bioprinting, Feinberg said.
Even 3D-printed tissues that are less complex than functioning organs may provide useful biological insights (Miller JS. PLoS Biol. 2014;12[6]:e1001882). In fact, the most immediate applications for 3D-printed tissues are research and drug testing, Feinberg said. For example, a company called Organovo has developed 3D-printed liver tissue for preclinical testing of drugs’ liver toxicity (http://bit.ly/1HAOjsN). Feinberg and his colleagues are currently working to build a 3D model of the mammary duct network that can be used to study ductal carcinoma in situ.
Miller predicted that regenerative uses of 3D-printed tissues will happen in the next 2 decades. One possibility might be implanting tissue scaffolds and letting the body do the rest.
Preclinical work toward this end has already begun. For example, a team of researchers 3D printed a biodegradable scaffold in the shape of a meniscus and impregnated it with growth factors to encourage stem cells to produce 2 different types of collagen (Lee CH et al. Sci Transl Med. 2014;6[266]:266ra171). Scaffolds infused with growth factors were implanted into live sheep that had undergone a partial meniscectomy. After several weeks, the meniscus regrew and the scaffold dissolved, leaving the sheep able to walk, whereas control sheep who received a scaffold without growth factors had difficulties walking.
“We don’t have to overengineer it,” Miller said. “There’s a lot of thinking about stimulating or inducing regeneration in the body.”