3D bioprinting–the additive manufacturing of tissues and organs–may be years away from use in your average hospital. But, as more animal trials prove successful, demand for the promise of customizable solutions offered by the technology is only growing.
“In the last year it’s gone from a handful of promising, but niche, applications to full blown chaos in terms of the rate of expansion,” said Scott Dunham, vice president of research at SmarTech Markets Publishing and a 3D printing industry analyst. “Medical professionals and non-medical professionals alike have taken the proven applications and technologies for medical 3D printing and have gone absolutely nuts with creating new potential treatments using 3D printing. It’s quickly infiltrating every area of the medical field.”
3D printing’s origins hark back to the 1980s. Today, the 3D printing medical market is expected to expand by 365% to $867 million by 2025, according to IDTechEx analysts. With the advancement of bioprinting, the medical market could reach up to $6 billion in 10 years.
The research is also widely expanding: From 2008-2011, the number of scientific papers referencing bioprinting nearly tripled. In August, Russian scientists announced the development of a magnetic 3D bioprinter that will allow production of living tissue on the International Space Station.
However, the potential of 3D printing is currently far greater than its actual use in medicine, despite the increasing number of successful clinical trials and peer-reviewed research emerging.
“The medical community is, by necessity, quite a slow thing to break into the mainstream,” Dunham said. “I would say that even by 2020, the level of acceptance will dwarf what we have already seen today.”
The latest projects from four universities show just how fast the field is developing.
Indiana University: Dermatology, ophthalmology, and cancer
Traditional 3D bioprinters use a scaffolded approach, creating objects in layers by applying a viscous cell-embedding substance known as a bio-ink through a nozzle. However, this process can sometimes kill the cells.
“There are proof of concepts of 3D bioprinting, but the field is struggling because it is in need of finding a bio ink that is compatible with the printing process,” said Nicanor Moldovan, associate research professor and director of the Bioprinting Core Facility of the Indiana University School of Medicine/Indiana University-Purdue University Indianapolis (IUPUI).
Enter the Regenova, which only IUPUI and Johns Hopkins University currently possess in the US. It is a 3D bioprinter that uses a robot to place the groups of cells, called spheroids, on a micro-needle array, allowing them to fuse together into a tissue. IUPUI was the first academic institute in the nation to receive one, in February 2016. The method of scaffold-free bioprinting may help speed FDA approval, Moldovan said.
It is especially useful for creating tube-like structures: Practically every tube in the body could be printed on the Regenova, as well as other cell-heterogeneous structures, he added. The team is currently developing tissue engineering and regenerative medicine projects in fields ranging from vascular and musculoskeletal biology to dermatology, ophthalmology, and cancer.
“The FDA wants to see the least departure from what is normal in an organism from the standpoint of biosafety and compatibility,” Moldovan said. “This doesn’t leave a biological signature behind–it’s just a way to keep the cells together until they fuse.”
Many investigators believe it will be at least 10-20 years before we see a truly meaningful medical application of 3D bioprinting, Moldovan said. He also said he does not think an FDA-approved construct will be available for at least five years.
Wake Forest University: Ears, bones and muscles
Regenerative medicine scientists at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina proved in a February paper that it is possible to print living tissue structures to replace injured or diseased tissue in patients.
The scientists printed ear, bone, and muscle structures. When implanted in animals, each part matured into functional tissue, and developed a system of blood vessels. These results indicate that the structures could eventually be used in humans, the researchers noted in Nature Biotechnology.
“This novel tissue and organ printer is an important advance in our quest to make replacement tissue for patients,” said Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine, and author of the study. “It can fabricate stable, human-scale tissue of any shape. With further development, this technology could potentially be used to print living tissue and organ structures for surgical implementation.”
Like IUPUI’s work, the Wake Forest team wanted to use a non-traditional printing approach to ensure the tissue cells would survive the process. Their answer was the Integrated Tissue and Organ Printing System (ITOP), which deposits biodegradable, plastic-like materials to form the tissue’s shape, and water-based gels that contain the cells. A strong, temporary outer structure forms, and does not harm the cells.
The scientists printed jaw bone fragments using human stem cells, which were the size and shape needed for facial reconstruction. The printed parts were implanted in rats, and after five months, they had formed vascularized bone tissue.
The Wake Forest team plans to implant bioprinted muscle, cartilage, and bone in patients in the future.
Pennsylvania State University: Cartilage plates
At Penn State, researchers created artificial cow cartilage using a 3D printer in June–and they have already begun experimenting with human cells.
Cartilage is a good tissue to target for scale-up bioprinting because it is made up of only one cell type, and has no blood vessels within the tissue. The team made tissue strands and fused them, so the structure assembled into a single piece of tissue resembling a cartilage patch.
Previous attempts at growing cartilage began with cells embedded in a hydrogel–a substance composed of polymer chains and about 90% water–that is used as a scaffold to grow the tissue. However, it made for less natural material, said Ibrahim Tarik Ozbolat, associate professor of engineering sciences and mechanics at Penn State University, and part of the Huck Institutes of the Life Sciences. In this work, the cartilage strand was used in place of hydrogel ink.
“The goal is to make something close to what we have in the body,” Ozbolat said. “Our product at the end will make a difference.”
The artificial cartilage produced by the team is very similar to native cow cartilage. However, the mechanical properties are inferior to those of natural cartilage–though still better than the cartilage that is made using hydrogel scaffolding.
Fat tissue harvested from patients at the Penn State Milton S. Hershey Medical Center will be broken down into stem cells, which scientists can differentiate into cartilage cells. The team is also awaiting approval to use rib cartilage, which a doctor at the medical center currently harvests during breast reconstruction surgery and discards.
While many universities are currently running 3D bioprinting trials, none have been approved by the FDA for use in humans, Ozbolat said.
Advanced Solutions Life Sciences (affiliated with University of Louisville): Capillaries and hearts
Advanced Solutions Life Sciences, in conjunction with the University of Louisville in Louisville, KY, is using 3D printed tissues to build one of the most important organs in the body: The heart.
“Bioprinting is one step of potentially many steps in a workflow,” said Jay Hoying, division chief of cardiovascular therapeutics at the Cardiovascular Innovation Institute at the University of Louisville, and a leader on their 3D bioprinting efforts. “If you’re going to start building complex tissues like a heart or liver, you’re not just going to print something up that’s shaped like a heart. You’re going to use printing and other assembly approaches to build the components of the heart, and bring them together.”
Hoying’s team is building capillary beds, which they can flow blood through in the lab. “We hope we can demonstrate this idea for living systems, and in the end have the basic platform to start adding different cell types and build tissues,” Hoying said. “Without a blood supply, whatever you’re going to build isn’t going to work.”
With one module–the capillaries–scientists can begin to add others, Hoying said. For example, perhaps they can add a liver module that’s vascularized and has blood flowing through it. Eventually, it might be possible to add a cardiac module, so that scientists could run a drug through the blood and have the liver metabolize it and see the impact on the heart.
Hoying envisions this technology will first be used testing medication.
“Once we have this ability to build capillary beds in the laboratory, we have the means to start building blood supplies to fabricate tissues,” he added. Eventually, it’s possible that the team could add up the pieces to create a fully-functional human heart.
However, many barriers remain between this work and mainstream medical use, the biggest being the biology itself, Hoying said. “If we start to see rudimentary heart-like constructs in my lifetime, we’ll be doing well,” Hoying said. “But stay tuned–it’s going to be changing pretty quickly.”
The 3 big takeaways for TechRepublic readers
- The 3D printing medical marketing is expanding rapidly, and expected to reach $867 million by 2025 thanks to its promise of creating customizable treatments and solutions for patients.
- Several US universities are currently running trials experimenting with building 3D printed tissues and organs.
- Despite the rapid growth in the field, no application has yet to receive FDA approval, and we are likely several years away from mainstream use in medical facilities.