The audiences at TED talks are used to being wowed as they learn about advances in technology. Even by TED standards, however, the 2011 presentation by Anthony Atala of the Wake Forest Institute for Regenerative Medicine was amazing. Unseen by the audience at first, various vials and nozzles hummed with mysterious activity behind Atala while he was on the stage. About two thirds of the way through the talk, a camera zoomed in on the device's internal armature and showed it weaving back and forth, depositing living cells grown in a laboratory culture layer by layer on a central platform, basing its activity on highly accurate three-dimensional digital renderings. The process, known as 3-D printing, resembles the operation of ink-jet printers but, in this case, instead of ink the printer uses a solution of living cells. In the end, Atala's machine produced, layer by layer, a life-size kidney made of human cells, much as a personal 3-D printer can spit out, say, a plastic replacement part for a coffeemaker.
A straightforward and quick way to make organs would be a welcome development for the more than 105,000 Americans waiting for organ donations. But the printed kidney Atala demonstrated two years ago was not ready to implant. It lacked two crucial elements: working blood vessels and tubules for collecting urine. Without these or other internal channels, large organs such as the kidneys have no way to get crucial nutrients and oxygen to, or remove waste products from, the cells deep within their interiors, and those cells quickly die. Researchers have tried to print these hollow structures layer by cellular layer into the organ by leaving holes in the right spots on each level, but the method produced conduits that can collapse and seams that can rupture under pressure from the blood being pumped by the heart.
A team of scientists from the University of Pennsylvania and the Massachusetts Institute of Technology has come up with a sweet solution to the problem. Instead of printing an organ and its inner vessels all at once, they print a dissolvable sugar mold of the vessels and then build up the appropriate cells around the mold. Later, the mold is washed away, leaving behind the structurally sound passageways that are able to stand up to the varying blood pressure levels found in the body.
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An Inspiring Dessert
The idea came to Jordan Miller (one of the lead researchers on the project and a postdoctoral fellow at Penn) in two stages. First, while visiting a display of preserved human cadavers and organs at a Body Worlds exhibit, he saw that preparators had exposed the lacelike structure of a large organ's vessels by injecting silicone into the vasculature and then dissolving away the remaining organic tissue.
Creating a synthetic mold on which to build internal vessels might work, Miller surmised, except that the chemicals needed to dissolve the silicone would be toxic to the living cells that were to be added. The way around that problem hit him when, at a fancy restaurant, he was served a dessert with an elegant hard-sugar lattice. Why not create a mold for an organ's blood vessels and other chambers out of sugar, which could be washed away with water?
Miller and his colleagues modified an open-source 3-D printer called the RepRap to print a carefully proportioned mixture of sugars in filaments of various sizes from about one millimeter down to 100 microns in diameter.
The team used these filaments to create an idealized version of a vascular network and coated the resulting sugar framework in a bio-friendly polymer to prevent the sugar from dissolving too fast. Then the scientists encased the whole thing in a combination of extracellular matrix [see “The Super Glue Cure,” on page 52] and endothelial cells of the kind that line blood vessels. Finally, the researchers eliminated the sugar with water, ending up with sturdy blood vessels made up of living cells.
Then it was the cells' turn. Just as they do in the body, they began remodeling the blood vessels in which they found themselves—giving the overall structure more strength and even creating tiny capillaries at the ends of larger vessels. By allowing the cells to fill in some of the details, says Christopher Chen, who runs the Tissue Microfabrication Lab at Penn, “we don't have to perfectly design the architecture.” In essence, the body can take over the finer touches on a nearly complete organ, allowing it to become fully functional.
To date, Chen, Miller and their colleagues have created blocks of liver tissue that contain sugar-molded blood vessels and implanted them in rodents to show that they will integrate with an existing vascular system. These slivers of tissue cannot take the place of a whole organ, but it is easy to see how adding liver, kidney or pancreatic cells on a fully developed vascular network could one day lead to the 3-D printing of larger body parts.
Learn more about regenerative medicine at ScientificAmerican.com/apr2013/regenerative-medicine