There’s plenty of excitement around the promise of machines that can spit out living cells patterned to create three-dimensional biological structures.
But the dream of functional 3-D-printed tissue and organs has long been stymied by a stubborn central challenge: how to get blood to flow to keep the cells alive.
Now, a team of researchers at the Wake Forest School of Medicine in North Carolina has made the latest contribution to solving the puzzle, though their findings are still a long way away from helping patients.
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The researchers devised a printing method that allowed them to fabricate bone, muscle, and cartilage tissues threaded with tiny channels where blood vessels developed when implanted in mice and rats. Most strikingly, this method worked with cartilage tissue the size and shape of a human baby’s ear, a structure much larger than would have been possible to sustain without blood flow.
“You’re basically creating a vascular network with a printer,” said Dr. Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine. He and his colleagues reported the findings Monday in Nature Biotechnology.
“They’re showing very elegantly in this work that we don’t need to over-engineer the system,” said Jordan Miller, a bioengineer at Rice University who was not involved in the study. The researchers got “functional tissue to emerge out of this provisional tissue they fabricated and implanted, which is just tremendously exciting.”
The Wake Forest team is one of many in mostly academic labs around the globe using molds to create a vascular system for 3-D-printed tissue.
Other researchers have demonstrated vascularization techniques like seeding channels with the cells that line the inside of blood vessels, or connecting implants directly in line with a rat’s artery. Atala and his Wake Forest colleagues tried a different tack: relying on the host animal’s healing systems to naturally fill the empty channels with blood vessels.
Figuring out how to pattern the rivers of microchannels is key to getting blood to flow properly between the layers of 3-D-printed cells because, without a blood supply, the dense layers of tissue found in complex organs won’t survive in any configuration that’s larger than about the thickness of a sheet of paper. That’s been “the basic limitation of this field forever up to this point,” Atala said.
By contrast, 3-D printing is increasingly being used in the clinic for things like customized knee and jaw replacements using plastics and titanium. Those medical and dental applications represented a more than $500 million global market in 2014, according to Wohlers Associates, a Colorado-based consulting firm focused on 3-D-printing.
But actually making something with living cells is a lot more challenging — and that’s slowed commercial development in the field significantly.
“Getting investors on board for a long-term experimental study that may not pan out … is a difficult proposition for venture capitalists right now,” Miller said.
Still, a few companies are still trying.
A Texas startup called TeVido BioDevices is looking to 3-D-print skin and fat cells to create nipple grafts for breast cancer survivors undergoing reconstructive surgery. That’s much simpler than trying to print something like muscle, and it’s allowed them to produce tissue at larger sizes than if they’d needed blood channels to keep cells alive.
But funding has been tough. Since its founding in 2011, the company has received only about $1.25 million, mostly from the US government’s Small Business Innovation Research program.
“That’s one of the things that’s limiting our progress, obviously,” said Scott Collins, the company’s president. But he’s optimistic about TeVido’s bet on simpler tissues until the technical capabilities for more complex tissues catches up.
Organovo, the world’s first publicly traded 3-D bioprinting company, is working with scientists at Yale University to solve some of these technical challenges to bioprinting human organs. But in the meantime, the San Diego firm is focused on selling 3-D-printed tissues for screening the toxicity of experimental drugs in the lab. “We’re trying to displace animal models,” said CEO Keith Murphy.
The company started by offering human liver tissue for drug testing in late 2014. Kidney models will be rolled out later this year. Organs suitable for surgical transplantation will take a decade or more.
The Wake Forest group’s next step is to do more testing in animals to assess whether their 3-D-printed tissue can survive and stay safe long-term. But Atala said it’s too early to talk about commercializing his team’s advance.
Companies “are just treading the water right now in terms of looking at these systems and seeing how well they work,” he said.
Elie Dolgin contributed reporting.