3-D printers make human tissue in push to create livers

3-D printing used to construct everything from art to toys to spare parts for the space station may one day produce human organs at a hospital near you.

The 20-year-old technology uses liquid materials that become hard as they print out three-dimensional objects in layers, based on a digital model. Current medical uses are in dentistry, for hard-material crowns, caps and bridges, as well as prosthetics. Last year, a 3-D printer was used to create a structure from moldable polymer that replaced more than 75 percent of a patient's skull.

Now, Organovo Holdings Inc. is using 3-D printers to create living tissue that may one day look and act like a human liver, able to cleanse the body of toxins. Drugmakers and cosmetic companies already plan to use 3-D printed human tissue to test new products. Eventually, the technology may help reduce organ shortages and cut transplant rejections as patients receive new organs constructed from their own cells.

“3-D printing is like a new tool set,” said Organovo Chief Executive Officer Keith Murphy. “You can make a living tissue you can grow outside the body. That's the core of our technology. How can you be smart about doing that?”

Organovo already is preparing to sell strips of liver tissue to drugmakers this year to be used to test toxicity of potential treatments, Murphy said in a telephone interview.

The San Diego-based company's five- and 10-year goals are first to use a patient's own cells to print tissue strips that can be used to patch failing organs, and finally to be able to create entire new organs.

$300 Printers

The first 3-D printer was produced in 1992. Since then, a variety of materials have been used as the technology has improved. The only limitation is that the printing material must be able to change from a liquid to a solid. Printers commercially available now sell for as little as $300.

Companies can save time and money using the printers to create customized products and single samples in-house rather than being ordered in from an outside manufacturer. To take that to an extreme, International Space Station astronauts plan to bring a 3-D printer to the craft this year, for making spare parts.

In 2012, the market for the 3-D products reached $777 million, and it may grow to $8.4 billion in 2025 as medical uses for the printers are developed, according to Anthony Vicari, an analyst at Lux Research Inc. in Boston.

The use of human cells works because of the natural tendency of the cells to stick together during embryonic development and move together in clumps with liquid-like properties. The first printing effort using cells occurred in 2003 using a modified ink-jet printer.

Drug Testing

Organovo will present data on test tissues for breast cancer and healthy kidneys by March 2015, Murphy said. That would lay the groundwork for tissue transplants, and eventually organ transplants, using 3-D printed cells.

Organovo's stock has mirrored its progress, more than doubling in the 12 months through last week. The shares gained 2.1 percent to $10.50 in New York trading on Feb. 21.

Murphy likened the technology to the early DNA work at Amgen Inc., where he spent 10 years developing drugs including the osteoporosis and bone cancer treatment Prolia, which is also marketed as Xgeva. In the early days, Thousand Oaks, California- based Amgen wasn't sure how best to use its ability to reprogram bacterial DNA until the company discovered it could create proteins for medical use, he said.

‘One-off Geometry'

“Dentures and replacing skulls, pretty much any time you need a one-off specific geometry, you can print it,” said Markus Buehler, a researcher at the Massachusetts Institute of Technology in Cambridge, in a telephone interview. “But most applications are fairly simple materials, and the kinds of materials we can print have, so far, been limited.”

Organovo, and researchers at academic centers such as the University of Toronto, would take the technology a step forward. In January, Organovo said it was collaborating with the U.S. National institutes of Health in helping scientists develop new tools to speed up the drug development timeline.

While early compounds are generally tested in small animals, that method has limitations, Murphy said. Using 3-D printed tissue will enable a researcher to quickly test many samples from different cell types, providing a more precise look at any possible problems, he said.

Genetic Differences

That means that not only can drugmakers test for the least- toxic medicines, they may also be able to show genetic differences in the treatments' effectiveness before testing in humans, he said. About one in 10 experimental drugs fail because of the toxicity, according to the U.S. Food and Drug Administration.

Organovo has already shown it can print out human liver tissue with the ability to process drugs like acetaminophen, commonly known as the painkiller Tylenol, Murphy said.

While functional liver cells for pharmaceutical testing are the current market, the production of organs should be possible after years of development, said Vicari, the Lux analyst.

“Organovo is the main leader in the printing of actual living tissue,” Vicari said in a telephone interview. “They've shown an impressive number of cells they can grow, and create tissue culture.”

Organovo isn't alone in its research push, said Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine in North Carolina.

Academic centers worldwide are trying to automate the method, so skin, cartilage, blood vessels and urethras can be printed for patients right where they're treated, Atala said by telephone.

Toronto Researchers

Researchers at the University of Toronto created thick layers of artificial skin for burn victims in June, using a cheap printer that may reduce the cost of skin transplants. The device, though, is still in a prototype stage, and its products haven't been tested in animals yet.

“Medical 3-D printing used to be more traditional: prosthetics, hearing aids, models for surgery,” said Jocelyn Phillips, an analyst at IBISworld, a New York-based research firm. “Those are traditional products, made of steel and plastic. Now we're seeing more companies looking into organs, blood vessels, skin, and those kinds of things.”

The main problem with 3-D printing organs instead of merely living tissue is creating a blood supply. Most organs have many cell types doing numerous jobs, and all those cells require nutrients and a way to extrude waste.

Blood Channels

Organovo has injected tissues with “filler” that can be removed and leave channels empty for blood. The challenge remains making very small blood vessels, called capillaries, that link the larger blood vessels to cells.

In the meantime, Organovo is exploring strips or tubes of cells that might be used to “patch” faulty organs, the CEO, Murphy, said. The strips are probably five to six years from clinical trials, although the tests may occur sooner if the cell types have already been used in similar trials, he said. Full- blown organs are further away, because of the problems with blood supply and structures.

“Organs are foreseeable, but that's a long-term goal,” Vicari said. “That requires not just the better printing technology, but much better understanding of tissue engineering.”