Scientists have developed an innovative 3D bioprinter capable of generating replacement tissue that’s strong enough to withstand transplantation. To show its power, the scientists printed a jaw bone, muscle, and cartilage structures, as well as a stunningly accurate human ear.
After nearly 10 years in development, a research team led by Anthony Atalafrom Wake Forest Institute for Regenerative Medicine has unveiled the Integrated Tissue and Organ Printing System (ITOP). Once refined and proven safe in humans, these 3D bioprinted structures could be used to replace injured, missing, or diseased tissue in patients. And because they’re designed in a computer, these replacement parts will be made to order to meet the unique needs of each patient. The details of this breakthrough were published today in Nature Biotechnology.
Bioprinters work the same way that conventional 3D printers do, using additive manufacturing to build complex structures layer by layer. But instead of using plastics, resins, and metals, bioprinters use special biomaterials that closely approximate functional, living tissue.
Credit: Wake Forest Institute for Regenerative Medicine
But existing bioprinters cannot fabricate tissues of the right size or strength. Their products end up being far too weak and structurally unstable for surgical transplantation. They also cannot print more delicate structures like blood vessels, or vasculature. Without these ready-made blood vessels, cells cannot be supplied with critical nutrients and oxygen.
“Cells simply cannot survive without a blood vessel supply that’s smaller than 200 microns [0.07 inches], which is extremely small,” Atala told Gizmodo. “That’s the maximum distance. And that’s not just for printing, that’s nature.” He said it’s the “limiting factor” that has made bioprinting a particularly challenging technological proposition.
Credit: Wake Forest Institute for Regenerative Medicine/Nature Biology
The new bioprinting system overcomes each of these shortcomings. Biodegradable plastic-like (polymer) materials are used to form the tissue shape, and a water-based gel delivers the cells to the structure (the gels aren’t toxic to the cells). A temporary outer structure helps to maintain the object’s shape during the printing process. To address the size limit, the researchers embedded microchannels into the design that allow nutrients and oxygen to be transported to cells anywhere within the structure.
Credit: Wake Forest Institute for Regenerative Medicine
“We basically recreated capillaries, creating microchannels that acted like a capillary bed,” said Atala.
Credit: Wake Forest Institute for Regenerative Medicine
To test their 3D-printed bio-parts, the researchers performed a number of experiments on live animals. Human-sized external ears were implanted under the skin of mice. After two months, the ears still maintained their shape, and cartilage tissue and blood vessels had formed. Printed muscle tissues were implanted in rats, and like the ears, they too maintained structural integrity.
Stem cells were used to create fragments of jaw bones, which were transplanted in rats. Five months later, the structures had formed vascularized bone tissue. In the future, 3D-printed bones could be used for facial reconstructions in humans.
Vascularization of a 3D printed ear after three months. Credit: Wake Forest Institute for Regenerative Medicine/Nature Biology
Atala said his team’s 3D-printed tissues appear to have the right size, strength, and function for use in humans. Their system can generate human-scale, structurally stable tissues in virtually any shape, and parts can be modeled in a computer according to the precise physical needs of a patient.
Immunofluorescent images show 3D printed muscle organization from one to three days. Credit: Wake Forest Institute for Regenerative Medicine/Nature Biology
Once the structures are proven safe and effective, the researchers can start to think about human trials. However, “We’re still looking at the safety of these things,” Atala conceded. “It’s still going to be a while—we still have to go through a lot of testing.”