10 Emerging Technologies That Will Change the World

TECHNOLOGY REVIEW

February 2003

Injectable Tissue Engineering

Every year, more than 700,000 patients in the United States undergo joint replacement surgery. The procedure-in which a knee or a hip is replaced with an artificial implant-is highly invasive, and many patients delay the surgery for as long as they can. Jennifer Elisseeff, a biomedical engineer at Johns Hopkins University, hopes to change that with a treatment that does away with surgery entirely: injectable tissue engineering. She and her colleagues have developed a way to inject joints with specially designed mixtures of polymers, cells, and growth stimulators that solidify and form healthy tissue. "We're not just trying to improve the current therapy," says Elisseeff. "We're really trying to change it completely."

Elisseeff is part of a growing movement that is pushing the bounds of tissue engineering-a field researchers have long hoped would produce lab-grown alternatives to transplanted organs and tissues. For the last three decades, researchers have focused on growing new tissues on polymer scaffolds in the lab. While this approach has had success producing small amounts of cartilage and skin, researchers have had difficulty keeping cells alive on larger scaffolds. And even if those problems could be worked out, surgeons would still have to implant the lab-grown tissues. Now, Elisseeff, as well as other academic and industry researchers, are turning to injectable systems that are less invasive and far cheaper. Many of the tissue-engineering applications to reach the market first could be delivered by syringe rather than implants, and Elisseeff is pushing to make this happen as soon as possible.

Elisseeff and her colleagues have used an injectable system to grow cartilage in mice. The researchers added cartilage cells to a light-sensitive liquid polymer and injected it under the skin on the backs of mice. They then shone ultraviolet light through the skin, causing the polymer to harden and encapsulate the cells. Over time, the cells multiplied and developed into cartilage. To test the feasibility of the technique for minimally invasive surgery, the researchers injected the liquid into the knee joints of cadavers. The surgeons used a fiber-optic tube to view the hardening process on a television monitor. "This has huge implications," says James Wenz, an orthopedic surgeon at Johns Hopkins who is collaborating with Elisseeff.

While most research on injectable systems has focused on cartilage and bone, observers say this technology could be extended to tissues such as those of the liver and heart. The method could be used to replace diseased portions of an organ or to enhance its functioning, says Harvard University pediatric surgeon Anthony Atala. In the case of heart failure, instead of opening the chest and surgically implanting an engineered valve or muscle tissue, he says, simply injecting the right combination of cells and signals might do the trick.

For Elisseeff and the rest of the field, the next frontier lies in a powerful new tool: stem cells. Derived from sources like bone marrow and embryos, stem cells have the ability to differentiate into numerous types of cells. Elisseeff and her colleagues have exploited that ability to grow new cartilage and bone simultaneously-one of the trickiest feats in tissue engineering. They made layers of a polymer-and-stem-cell mixture, infusing each layer with specific chemical signals that triggered the cells to develop into either bone or cartilage. Such hybrid materials would simplify knee replacement surgeries, for instance, that require surgeons to replace the top of the shin bone and the cartilage above it.

Don't expect tissue engineers to grow entire artificial organs anytime soon. Elisseeff, for one, is aiming for smaller advances that will make tissue engineering a reality within the decade. For the thousands of U.S. patients who need new joints every year, such small feats could be huge. - Alexandra M. Goho

Others in 
INJECTABLE TISSUE ENGINEERING RESEARCHER PROJECT Anthony Atala 
Harvard Medical School Cartilage Jim Burns 
Genzyme Cartilage Antonios Mikos 
Rice U. Bone and cardiovascular tissue David Mooney 
U. Michigan Bone and cartilage