A device the size of an espresso machine quietly whirs to life. The contraption isn’t filled with fresh, pungent grounds but, instead, spoonfuls of opaque, sterile goo. Its robotic arm moves briskly: It hovers, lowers, and then repositions a pair of syringes over six petri dishes. In short, rapid-fire bursts, they extrude the milky paste. Soon, three little hexagons form in each dish. After a few minutes, the hexagons grow to honeycomb structures the size of fingernails. No one here is getting a latte anytime soon.
The honeycombs are human livers, says Sharon Presnell, chief technology officer of Organovo—or at least the foundations of them. The tiny masterpieces of biomedical engineering are nearly identical to tissue samples from real human livers, and they are constructed from actual human cells. But instead of growing them, scientists in the gleaming, 15,000-square-foot headquarters of Organovo print them, just as they would a document. Or, more accurately, just as they’d print a scale model.
In two decades, 3-D printing has grown from a niche manufacturing process to a $2.7-billion industry, responsible for the fabrication of all sorts of things: toys, wristwatches, airplane parts, food. Now scientists are working to apply similar 3-D–printing technology to the field of medicine, accelerating an equally dramatic change. But it’s much different, and much easier, to print with plastic, metal, or chocolate than to print with living cells.
“It’s been a tough slog in some ways, but we’re at a tipping point,” says Dean Kamen, founder of DEKA Research & Development, who holds more than 440 patents, many of them for medical devices. In labs around the world, bioengineers have begun to print prototype body parts: heart valves, ears, artificial bone, joints, menisci, vascular tubes, and skin grafts. “If you have a compass and a straight edge, everything you draw is a box or a circle,” Kamen says. “When you get better tools, you start thinking in different ways. We now have the ability to play at a level we couldn’t play at before.”
From 2008 to 2011, the number of scientific papers referencing bioprinting nearly tripled. Investment in the field has spiked as well. Since 2007, the National Heart, Lung, and Blood Institute of the National Institutes of Health has awarded $600,000 in grants to bioprinting projects. Last year, Organovo, raised $24.7 million in equity.
Three factors are driving the trend: more sophisticated printers, advances in regenerative medicine, and refined CAD software. To print the liver tissue at Organovo, Vivian Gorgen, a 25-year-old systems engineer, simply had to click “run program” with a mouse. Honeycomb-shaped liver tissue is a long way from a fully functioning organ, but it is a tangible step in that direction. “Getting to a whole organ-in-a-box that’s plug-and-play and ready to go, I believe that could happen in my lifetime,” says Presnell. “I cannot wait to see what people like Vivian do. The potential is just out of this world.”
The very first bioprinters weren’t expensive or fancy. They resembled cheap desktop printers because, in fact, that’s what they were. In 2000, bioengineer Thomas Boland, the self-described “grandfather of bioprinting,” eyed an old Lexmark printer in his lab at Clemson University. Scientists had already modified inkjet printers to print fragments of DNA, in order to study gene expression. If an inkjet could print genes, Boland thought, perhaps the same hardware could print other biomaterials. After all, the smallest human cells are 10 micrometers, roughly the dimension of standard ink droplets.
Boland emptied the Lexmark’s ink cartridge and filled it with collagen. He then glued a thin, black silicon sheet onto blank paper and fed it into the printer. He opened a Word document on his PC, typed his initials, and hit print. The paper spooled out with “TB” clearly delineated in off-white proteins.
By 2000, Boland and his team had reconfigured a Hewlett-Packard DeskJet 550C to print with E. coli bacteria. Then they graduated to larger mammalian cells, farmed from Chinese hamsters and lab rats. After printing, 90 percent of the cells remained viable, which meant the product was useful, not simply art. In 2003, Boland filed the first patent for printing cells.
While Boland’s lab worked out the problem of bioprinting, other engineers applied 3-D printers to different medical challenges. They printed bone grafts from ceramic, dental crowns from porcelain, hearing aids from acrylic, and prosthetic limbs from polymer. But those engineers had an advantage that Boland and his colleagues did not: They could print in three dimensions rather than just two.
So Boland and other bioprinting pioneers modified their printers. They disabled the paper-feed mechanisms in their inkjets and added an elevator-like platform controlled by stepper motors; the platform could move up or down along the z-axis. Labs could print one layer of cells, lower the platform, and print another layer. Suddenly, bioengineers went from drawing life on a flat canvas to building living sculptures.
“It was like magic,” says James Yoo, a researcher at the Wake Forest Institute for Regenerative Medicine who is developing a portable printer to graft skin directly onto burn victims. The ability to print cells in three dimensions opened up new applications. “Every wound is different; the depth is different; and they’re very irregular,” Yoo says. “By mapping the area, you can determine how many cell layers are needed for the subdermal tissue, as well as the epithelial area. The advantage of the printer is that you can deliver cells more accurately and precisely.”
Scientists could also print with many types of “ink.” Cornell engineer Hod Lipson, co-author of Fabricated: The New World of 3D Printing, prototyped another kind of tissue: cartilage. “The spatial control over the placement of cells has never been possible to this degree,” he says. “That opens up multiple dimensions of possibilities.” Lipson and his colleagues decided to print a meniscus, the C-shaped piece of cartilage that cushions the knee and other joints. The team used CT scans to create a CAD file of a sheep’s meniscus and extracted cells from the sheep to print an identical one.
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