Organs on Demand
3-D printing has made inroads in the clinic, but constructing functional complex organs still faces major hurdles.
On a stage in front of an audience of thousands, a futuristic-looking machine squirted gel from a nozzle. Layer by layer, it built up the material, shaping it into a curved, pink, kidney-shape structure based on a medical CT scan of a real organ.
It was 2011, and Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine, was demonstrating his progress in using three-dimensional (3-D) printing to make a kidney during his TED Talk. Like a TV chef pulling a previously baked casserole from the oven, Atala soon held a bean-shape object in his gloved hands. “Here it is,” he said. “You can actually see the kidney as it was printed earlier today.” The audience erupted into cheers.
But Atala had not made a functional human kidney, as he at times seemed to imply and as the Agence France-Presse reported in a widely disseminated article. “A surgeon specializing in regenerative medicine … ‘printed’ a real kidney using a machine that eliminates the need for donors when it comes to organ transplants,” it read.
Wake Forest quickly tried to stem the misleading coverage. “Reports in the media that Dr. Anthony Atala printed a real kidney at the TED conference in Long Beach, Calif., are completely inaccurate,” stated a press release issued by the university following the media coverage. Rather, Atala had printed only a kidney-shape “mold” made of biocompatible materials combined with cells. The prototype, as Atala calls it, lacked the kidney’s intricate inner structures, such as the fine networks of vessels called glomeruli that allow the organ to filter waste materials from the blood. The prototype could not have functioned as a real organ and thus was not ready for transplantation prime time; that may only be possible “many years from now,” cautioned the press release.
Atala’s kidney prototype represents both the promise of 3-D printing in a medical context and the hurdles that tissue engineers have yet to clear. With recent technological advances, using 3-D printing to shape gels embedded with living cells into the general form of organs has become a relatively achievable task. Printing a liver or a kidney that functions in the same way and with the same efficiency as a real organ, however, is a different story. The most formidable obstacle standing in the way of functioning 3-D–printed organs is the difficulty of replicating the branching networks of veins, arteries, and capillaries that nourish the body’s tissues and filter out waste. In most organs, cells must be within 150 to 200 microns—the width of a few human hairs—of the nearest capillary to survive.
As researchers modify and build devices that print with ever greater precision, and invent new biomaterials to serve as ink for these machines, they have been able to make substantial progress on printing ears, spinal discs, heart valves, and bone, which are moving towards the clinic. (See illustration below.) Similarly, simple engineered tissues, such as tracheas and bladders made from cells seeded onto biocompatible scaffolds and created without the use of 3-D printing, have already been inserted into patients. But these tissues have thrived only because they are thin enough not to require extensive infiltration by blood vessels.
“[Vascularization has] been something that’s been worked on for 20 years,” says Jennifer Lewis, a materials engineer at Harvard University who is designing printers she hopes will produce vascularized tissues. “It’s plagued a number of advances.”
Achieving vascularization may be the biggest challenge that faces researchers attempting to 3-D print organs, but 3-D printing could also be the very technology to solve this problem. Researchers are harnessing 3-D printers to build tiny, hierarchical networks of blood vessels to supply increasingly complex 3-D–printed organs with blood.
“For me the holy grail of tissue engineering is to fabricate tissues with their own vascular network,” says Jason Spector, an associate professor of plastic surgery at Weill Cornell Medical College, who is working on printing ears and other tissues. “Once you can make that, everything else is cake.”