Scaling Up
This isn't the first bio-3D printer, but previous devices have been quite limited by the size of the living tissue they can create. That's because most living tissues need an influx of blood and nutrients to stay healthy, but 3D tissue printers aren't nearly advanced enough to print complex features like arteries and blood vessels. So by printing, say, a thick sphere of cartilage, you'd be sure to starve the cells trapped inside. According to Atala, until today the largest printed structure that could be kept alive without blood-cells was only 0.007 inches thick. That's about twice the size of a grain of salt.
ITOP, though, gets around this size limitation by fabricating a latticework of microscopic valleys into the bone, muscle, and cartilage it prints. Supported by the biodegradable plastic scaffolding, these valleys allow nutrients and blood to flow in, keeping tissues alive for months before they're implanted, and "indefinitely," after implantation, Atala says.
"This process allows the tissues we print to keep the structural integrity necessary to implant inside the body."
The team has shown that ITOP can print a impressive suite of living materials. In their demonstrations, the scientists crafted infant-sized ears of cartilage, chunks of replacement jawbone and shards of skull bones, and strips of muscle. Although these tissues are one-dimensional in that they're all crafted from stem cells that develop into a variety of different cell types, "the tissues mature to the same level as normal tissue would," says Atala.
The team has now implanted some of this bone, cartilage, and muscle tissue to great success. But not into humans—yet. In a weird throwback to the Vacanti mouse, the researchers printed an infant's ear of rabbit cartilage under the skin of a mouse, and let it grow. Months after implantation, the cartilage still looks just like an ear, and the mouse's body had started to attach and grow blood-vessels on it. A similar process happened with rat-implanted bone printed from human stem cells: Veins started to take hold.
Two weeks after implanting a strip of printed muscle in a rat, Atala's team found that it likewise started to thrive. While it only weakly responded to electric prodding (the researchers liken it to immature, developing muscle) the muscle started to grow both blood vessels and nerves.
For now, Atala's team is testing the long-term safety of ITOP's approach as a run-up to developing tissues for human implantation. In the future, the researchers hope to work with stem cells taken directly from a patient. But Atala believes that for some simple tissues like bone, the theoretical barriers for 3D printing customized replacement parts (say, a new kneecap, hot of the press) may be barriers no more.
