Sitting in his Rice University lab back in 2013, assistant professor Jordan Miller was trying to 3-D print part of a human organ when he identified his solution as yellow. Unfortunately, yellow was also his obstacle.
While this sounds like the plot of a children’s picture book, color is an issue the bioengineer had regularly considered in his work using a light-based 3-D printer. A special liquid tinted with yellow would turn into a solid gel when a blue light shone on it, creating a two-dimensional layer in about ten seconds—zap. A machine could print and stack these two-dimensional scans, forming a three-dimensional structure. And a breakthrough in 3-D printed organs was at stake.
The question was: which yellow supplement was suitable to represent a living thing? Miller knew about a dye called Sudan 1 that worked in a 3-D printer, but the pigment didn’t dissolve in water, it was toxic, it was carcinogenic—not exactly the kind of material people wanted surgically implanted into their bodies. Brainstorming with his graduate student, Bagrat Grigoryan, Miller turned to Grigoryan and asked, “What about food coloring?”
Miller, 39, has a boyish quality about him; he talks about the body with enthusiasm, reverence, and awe, as if he were discussing an architectural marvel. “You have a beautiful airway,” he told me, excitedly, “ensheathed by a very complicated blood vessel structure.” Miller was particularly interested in airways and blood vessel structures because of the form his lab had decided to create: an air sac—a mechanically complicated component that provided a relatively simple measuring stick; either it oxygenated blood or it didn’t. Creating an air sac had proved elusive to everyone in Miller’s field.
It was, at least, until Miller bought some packets of food coloring at an H-E-B in the city’s Montrose neighborhood, and Grigoryan mixed the liquid into the lab’s special mixture. Grigoryan turned on the 3-D printer, and the two men listened to the printer hum softly as they waited for the results. Forty minutes later, when the printer signaled that it was finished, Grigoryan held up the rudimentary model. “It was definitely a wow moment,” Miller told me. It was the first in a series of victories. About a year later, the lab created a ten-millimeter-long air sac that looked like a tiny, clear, bulbous purse, and Grigoryan blew the debris off the newly born, squishy, gelatinous structure with a can of pressurized air. Stunningly, Miller and his team found, red blood cells could absorb oxygen as they flowed through the synthetic air sac—performing the same function as a human lung’s alveolar air sacs.
This past May, Miller and his team published their paper “Multivascular networks and functional intravascular topologies within biocompatible hydrogels” to much acclaim, with extensive implications. Almost 115,000 American patients are waiting for organ transplants. Using 3-D printed organs as scaffolding, scientists will be able to rebuild patients’ whole organs using their own cells. Doctors won’t be able to use this technology immediately—to create a whole lung, Miller will need about 600 million more air sacs—though in the next five years, Miller envisions that small 3-D printed implants could work as a “patch” to keep patients’ organs working as they wait for full organ transplants. It all sounds like science fiction.
But the least predictable aspect of Miller’s project is the one with the deepest philosophical impact: the design. In creating the air sac, Miller says, he and his partnering scientists constructed biologically compatible architecture that didn’t imitate a human model. “Do we need to make something that’s identical to the organs in the body or is something that’s functionally equivalent going to be as effective?” he asked. “It’s interesting.”
While the blueprints for organs would likely be inspired, at least in part, by humans, they could also incorporate elements from other species. Human lungs are efficient, Miller pointed out, but they’re not as efficient as, say, bird lungs. And bird lungs aren’t as efficient as bat lungs. Fish gills efficiently employ something called countercurrent flow, pumping blood forward toward a fish’s head while the water is rushing backward over its gills.
To be clear, Miller isn’t suggesting that he’d give someone actual bird lungs or fish gills—only that he’d borrow design elements from them. Ideas could come from outside the animal kingdom as well, in the same way that a prosthetic leg running blade acts more like a spring than a foot. Some of the designs used in Miller’s air sac, for example, were derived from the vein patterns present in leaves. Other elements are derived from waterfalls. “You have the tiny tributaries draining into the bigger vessels,” he said, “and there are ways to mimic those phenomena in the lab and in the computational side to get things that will resemble some other vascular architecture and hierarchies that we see in the body.”
This idea isn’t novel: for decades, mathematicians have been studying biological structures, figuring out their efficiencies. What’s new is seeing that math come to life in this project. “It’s not just a step forward on the engineering side,” he says, “but another step forward in the design side, because we really need better blueprints to generate living tissue.”
“There may be more than one solution to architecting human organ replacement,” Miller adds. “And that’s a very exciting proposition.”