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Tissue.prn: Desktop Printer Technology Used to Lay Down Regenerated Skin Cells to Treat Burns in Mice

The same technology that office workers use daily to print documents can be transformed into a "bioprinter" that uses cells instead of ink



Wake Forest University

The same printer technology that sits on your desk could soon be a common fixture in rebuilding human tissue, treating burns by laying down layers of a patients' own skin or even rebuilding whole organs.

A team at Wake Forest University has built a "bioprinter" that uses cells instead of ink. It even uses an ordinary, off-the-shelf printhead, connected to test tubes full of different cell types instead of wells full of colored inks.

Led by Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine in Winston–Salem, N.C., the team is working on treating burns. Such wounds can be hard to treat, because in severe cases there might not be enough healthy skin on the patient to harvest or culture for a graft. Grafting skin to cover burn wounds is also important for preventing infections, which can be a source of complications. Printing out cells grown in culture would eliminate these problems. Another application is repairing scar tissue.

Currently, grafts are either sheets of skin taken from a donor site on the body, or layers of cells cultured in vitro from the patient. But the latter technique is not always successful as the skin cells grown in vitro must be handled carefully and the skin can break down or contract.

To treat burns, a laser would scan the wounded area and create a three-dimensional map that would be transmitted to the printer. The print head would lay down the cells layer by layer, directly on the burn.

The project is part of an $85-million U.S. Department of Defense program to apply regenerative medicine to battlefield injuries. The military is particularly interested because 10 to 30 percent of battlefield deaths result from burns.

Atala says the idea of building objects with a printer has been around for some time. He noted the idea was borrowed from computer-aided design (CAD), which for many years has translated 3-D models from the screen to prototypes. Using this technique for tissue engineering, he says, has been studied for decades.

The breakthrough in using bioprinting for tissue regeneration is the gel used to contain the cells: The mixture must hold the cells in place when they are laid down as well as provide a viable medium where they can be kept alive while they are held in the reservoirs. "It took us seven years," he says. "There's lots of trial and error; this isn't trivial chemistry," he adds.

For building tissue, several printing methods were tried, including three-dimensional CAD and laser printing. But once the group hit on the inkjet method, it turned out to work so well that some of the early work on building tissue was done on modified inkjet printers from a local office supply store.

Other organs have been constructed from cultured cells, but they were built on a scaffolding to give them their three-dimensional shape. Skin doesn't require a matrix because it is relatively flat to begin with.

So far, the system has been tested on mice, which are given wounds similar to burns. Those that were treated with printer-generated cells healed in three weeks, whereas those that were allowed to recover naturally required five weeks. The researchers plan to test the system on bigger animals in the future. The technology is still in the early stages, Atala says. As of yet there is no timetable for human tests or for the publication of the mouse research results.

The Wake Forest group is not just working on skin. Bone tissue and a two-chambered mouse heart have both been successfully printed. The heart was stimulated to beat when the cells were shocked with electricity, and the printed bones have been implanted in mice.

But one challenge with printing out organs—a heart, for example—is that they require connections to blood vessels, nerves and other tissue in order to function properly. So although it is possible to get mouse heart cells to twitch with an electrical jolt, it is not yet possible to grow the necessary connections to the rest of the body while the new heart is put in place. Regenerated skin tissue, however, is different: After it is grafted it absorbs plasma, and blood vessels eventually grow into it.

Vladimir Mironov, an assistant professor in the department of Regenerative Medicine and Cell Biology at the Medical University of South Carolina, says the big contribution from Atala is the use of living cells. "It's a new page in tissue engineering, the use of cells in vivo," he says. By focusing on skin, Mironov says Atala has avoided some of the problems associated with printing whole organs, and by printing living cells directly on the wound, the fluid suspending the cells is absorbed.

Mironov says one part about which he is skeptical at this point is how well the process works on large areas and on different skin types. Another issue is how to grow enough cells if a burn covers a very large area; the cells would have to be taken from the patient's skin so as to avoid rejection, so they would likely need to be grown in advance of printing them, which can take some time. That may not be practical in some cases.

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