Scientists are developing a way to treat arthritic hips without extensive surgery to replace them. They’ve programmed stem cells to grow new cartilage on a 3D template shaped like the ball of a hip joint.
What’s more, using gene therapy, they have activated the new cartilage to release anti-inflammatory molecules to fend off a return of arthritis.
The discovery may one day provide an alternative to hip-replacement surgery, particularly in younger patients. Doctors are reluctant to perform such operations in patients younger than 50 because prosthetic joints typically last for less than 20 years. A second joint-replacement surgery to remove a worn prosthetic can destroy bone and put patients at risk for infection.
“Replacing a failed prosthetic joint is a difficult surgery,” says Farshid Guilak, professor of orthopedic surgery at Washington University. “We’ve developed a way to resurface an arthritic joint using a patient’s own stem cells to grow new cartilage, combined with gene therapy to release anti-inflammatory molecules to keep arthritis at bay. Our hope is to prevent, or at least delay, a standard metal and plastic prosthetic joint replacement.”
Listen to Farshid Guilak describe the new technique:
The technique uses a 3D, biodegradable synthetic scaffold that is molded into the precise shape of a patient’s joint and is covered with cartilage made from the patient’s own stem cells taken from fat beneath the skin. The scaffold can then be implanted onto the surface of an arthritic hip, for example.
Resurfacing the hip joint with “living” tissue is designed to ease arthritis pain, and delay or even eliminate the need for joint-replacement surgery in some patients.
Additionally, by inserting a gene into the newly grown cartilage and activating it with a drug, the gene can orchestrate the release of anti-inflammatory molecules to fight a return of arthritis, which usually is what triggers such joint problems in the first place.
“When there is inflammation, we can give a patient a simple drug, which activates the gene we’ve implanted, to lower inflammation in the joint,” says Guilak, who is also a professor of developmental biology and of biomedical engineering. “We can stop giving the drug at any time, which turns off the gene.”
How to weave the fabric
That gene therapy is important, he explains, because when levels of inflammatory molecules rise in a joint, the cartilage is destroyed and pain increases. By adding gene therapy to the stem cell and scaffold technique, researchers believe it will be possible to coax patients’ joints to fend off arthritis and function better for a longer time.
The 3D scaffold is built using a weaving pattern that gives the device the structure and properties of normal cartilage. Franklin Moutos, vice president of technology development at Cytex, explains that the unique structure is the result of approximately 600 biodegradable fiber bundles woven together to create a high-performance fabric that can function like normal cartilage.
“As evidence of this, the woven implants are strong enough to withstand loads up to 10 times a patient’s body weight, which is typically what our joints must bear when we exercise,” he says.
Currently, there are about 30 million Americans who have diagnoses of osteoarthritis, and data suggest that the incidence of osteoarthritis is on the rise. That number includes many younger patients—ages 40 to 65—who have limited treatment options because conservative approaches haven’t worked and they are not yet candidates for total joint replacement because of their ages.
“We envision in the future that this population of younger patients may be ideal candidates for this type of biological joint replacement,” says Bradley Estes, vice president of research and development at Cytex.
Guilak has been collaborating with Cytex on this research. The scientists have tested various aspects of the tissue engineering in cell culture, and some customized implants already are being tested in laboratory animals. If all goes well, such devices could be ready for safety testing in humans in three to five years.
The National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute on Aging of the National Institutes of Health funded the work.
Guilak and collaborators have a financial interest in Cytex Therapeutics of Durham, N.C., which holds patents for the development of these devices. They could realize financial gain if the devices eventually are approved for clinical use.