One of the holy grails of medicine — implanting major organs created from a patient’s own cells — may be many years away, but 3-D printing technology is already being used to create functional human tissue and bone-like implants, along with life-saving treatments and tools used in surgery.

It goes well beyond the guitars, guns and other colorful objects often used to illustrate the recent 3-D printing boom.

According to the 2013 Wohlers Report, a review and analysis of the 3-D printing industry worldwide, $361 million of the more than $2 billion in revenue the industry generated in 2012 came from 3-D printing for medical and dental uses.

There are two major types of medical 3-D printing. One type, bioprinting, uses a combination of hydrogels and human cells to build tissue in a specific shape, layer by layer, while the more traditional process of making solid 3-D objects from a digital blueprint is used to create everything from orthopedic implants to hearing aids.

San Diego-based startup Organovo, which grew out of discoveries made at the University of Missouri, has been working on the bioprinting side, using a proprietary 3-D printing process to make functional human liver tissue that pharmaceutical companies can use to test toxicity. While the small strips of liver tissue the company prints don’t have all the anatomy and function of implantable tissue, they provide much more precise results than the two-dimensional cell cultures companies use to test drugs during the early stages of development, says Michael Renard, Organovo’s vice president of commercial operations.

Testing with 3-D tissues can give the pharmaceutical companies more precise results and let them make smarter decisions about investing more in costly clinical trials.

“It would be very advantageous to add that human liver model into their lab testing as a way to give them greater confidence to make that decision to go into humans and spend more money,” Renard says.

The company’s longer-term goal is to use the technology in patient care, developing tissues from a patient’s own cells that can be used in direct surgical therapy: things such as heart muscle patches, nerve grafts, or blood vessels for bypass.

Printing kidneys
Dr. Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine in North Carolina, is somewhat of a rock star in the regenerative medicine world. In a 2011 TED talk, he wowed the audience by showing off a kidney that had been printed backstage, based on a CT scan of an actual organ. Though the printed kidney could not actually filter blood, it was a glimpse at what is likely possible in the future.


At a 3-D printing conference in New York City last month, Atala spoke about how scientists at the Wake Forest Institute for Regenerative Medicine are working on a machine designed to print skin cells onto burn wounds, along with a scanner used to determine wound size and depth. The research is part of a grant funded by the Department of Defense, with the idea that this treatment can be used on the battlefield.

“It really makes a great difference when you bioprint,” Atala said during a talk on regenerative medicine at the conference. “You know exactly where to lay the cells down.”

The institute is also leading a $24 million federally-funded project to develop a “body on a chip,” creating tiny organ-like structures that will be used to model the body’s response to harmful chemical and biological agents and develop potential treatments.

While Atala, a urologist, already led a team that grew and implanted a human bladder and urethra using a scaffold seeded with human cells, he notes that creating solid organs, such as a heart, liver or kidney, that can be implanted in patients and solve the organ-donor shortage, is still a ways off. “Those require much more vascularity to survive long term,” Atala says.

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard School of Engineering and Applied Sciences (SEAS) seem to have taken a step in that direction. They recently developed a new bioprinting method to create 3-D tissue with multiple types of cells and even tiny blood vessels. The results were reported in February in the journal Advanced Materials.

“It’s really the only way to go to thicker tissue,” says lead author David Kolesky, a graduate student in SEAS and the Wyss Institute. “If you don’t have a way to deliver nutrients to the center of your tissue, they’re going to be oxygen-stressed and they’re going to die.”

Kolesky says that while this is definitely a step toward creating functional, solid organs, like a kidney, that is still years away. His team is mainly looking at how this tissue can more realistically test drug safety and effectiveness.

“We are adding a level of complexity to the printed tissue that isn’t there if you only have a single cell type present,” Kolesky says.

What can be implanted
In 2012, doctors at the University of Michigan obtained emergency clearance from the U.S. Food and Drug Administration and implanted a 3-D printed splint in a three-month-old boy suffering from a severe case of tracheobronchomalacia, a rare condition in which the airways collapse during breathing and coughing.



“3-D printing really allows fine structures to be put in place that you can’t get by hand, so true engineering can be applied to it,” Dr. Glenn Green, associate professor of pediatric otolaryngology at the University of Michigan, told DOTmed News last year.

3-D printing technology allows for rapid manufacture of small numbers of parts with precise detail. The technology has also evolved to create very fine facial features. In Wales, a team of surgeons and design engineering experts has been using 3-D printing in complex mid-facial reconstruction surgeries. The Centre for Applied Reconstructive Technologies in Surgery (CARTIS) — a partnership between staff at the Maxillofacial Unit at Morriston Hospital in Swansea, Wales, and the National Centre for Product Design and Development Research at Cardiff Metropolitan University — worked together for a recent high-profile operation on a man whose face had been crushed in a 2012 motorcycle accident, using custom-printed prototype bone models, surgical guides and implants.

The team used CT scans to create a computer model, which was used to plan the operation, based on restoring facial symmetry by cutting and moving sections of bone. Cutting and re-positioning guides, and custom implants were then designed and 3-D printed in metal. These tools enabled the computer plan to be translated into surgery by accurately guiding the surgeon’s instruments and enabling the separate bone sections to be located and fixed in the correct position.

Dr. Dominic Eggbeer, head of surgical and prosthetic design at Cardiff Metropolitan University, says it was a particularly challenging case. “You have to cut the bones in a very precise way, and move them in a very precise way, and fix them in a very precise way,” Eggbeer says.

The university takes on about 500 cases a year across the UK, mainly head and neck reconstruction, such as fixing large defects in skull and implanting small devices in the mid-face. The design staff uses software from South Carolina company 3D Systems.

The reconstruction process begins with a CT scan, which is turned into a 3-D image based on the bony tissue anatomy. Next, the surgeon provides input on how they want to do the reconstruction.

“It’s up to us to interpret that surgical intent to the optimal design solution and produce iterations that can be validated onscreen or printed,” Eggbeer says.

They print using a polymer for testing, and then use more expensive metal materials once the prescribing surgeon signs off on the final design.

It’s definitely a team effort, and the challenge comes in working with the surgeons to make sure they understand both the potential and the constraints of these technologies. “There’s a gap between what surgeons see as possible and what engineers see as possible with the same technology,” Eggbeer says. “It’s one thing to create the perfect engineered body part on the computer screen, but that’s not always perfect for the surgery.”

While the technology to print implants that provide structural support is mostly there, there are still advances to be made. At the same Inside 3D Printing Conference where Atala spoke, Dr. Amir Dorafshar, assistant professor of plastic and reconstructive surgery and clinical co-director of the face transplant program at Johns Hopkins Medicine, mentioned some of the limitations.

In some cases, doctors have taken bones with blood supply from a patient’s leg to aid in facial reconstruction. Dorafshar has also been involved in face transplants, including a major one in 2012 involving a man whose face had been damaged in a gun accident. But if face transplants aren’t futuristic enough, Dorafshar says they’re moving toward creating scaffolding printed in 3-D with a vascular structure.

“In the future, we hope to have a mask 3-D printed from the donor face,” Dorafshar says. “For a face transplant case, where we take the face of a donor to place on a recipient of another, we end up with a large defect on the donor. This can be reconstructed more readily with a 3-D implanted face to preserve the donor’s dignity.”