"New Fixes for Worn Knees" - The Wall Street Journal
New Fixes for Worn Knees
By Melinda Beck
Scientists have created artificial replacements for arms, legs, joints and other body parts. But developing an artificial meniscus—the shock-absorbing cartilage pad in the knee that millions of people damage every year—has eluded modern medicine.
Researchers are now tantalizingly close to achieving that goal, a step that could help stave off more serious problems, including arthritis and knee-replacement surgery, in later years.
Drake Ross, a 54-year-old bank examiner in Columbus, Ohio, this year became the first American to have a synthetic meniscus, called NUsurface, implanted in his knee as part of a clinical trial.
And scientists from New York’s Cornell and Columbia universities have successfully tested in sheep a method of growing a new meniscus inside the knee joint using a 3-D printer and the body’s own stem cells. They hope to begin testing the technique in people soon.
Either method would be a “game changer—no question,” says Nicholas DiNubile, a knee specialist in Havertown, Pa., and a spokesman for the American Academy of Orthopaedic Surgeons. “But it’s a tall order. You’re trying to replace Mother Nature here. We’ve been burned before.”
There is plenty of demand for replacement menisci. The crescent-shaped pads (there are two in each knee) that separate the thigh and shin bones act as shock absorbers and stabilizers as people walk, run, pivot and bend. But they are highly vulnerable to tearing, particularly by athletes who jump, twist and stop suddenly.
The rubbery cartilage also wears down and tears easily as people age or carry excess weight. More than four million Americans visited physicians for meniscus tears in 2009, the latest numbers available, twice as many as in 2000, according to the AAOS.
Many meniscus tears are minor and go unnoticed, studies show. Others cause pain, stiffness and swelling, and fragments may catch or slip as the knee moves and can tear further. Tears that occur near the outer edge can be sutured but the inside of the meniscus has no blood supply so repairs there seldom heal. Instead, doctors cut away the ragged portion and smooth the remainder. Nearly one million such surgeries are performed each year.
A partial meniscectomy, as it is called, can alleviate pain, but it puts patients at high risk for arthritis. That is because where the meniscus is missing, the cartilage covering the ends of the leg bones rubs together and frays. Eventually that may leave bone rubbing against bone, which often requires a knee replacement. More than 700,000 Americans undergo a knee replacement each year. That is expected to grow to 3.5 million by 2030 as the population ages, according to the AAOS.
Young athletes who have meniscus surgery in their teens and develop arthritis in their 20s are especially in need of new options. Artificial joints typically last only 15 years to 20 years, and a second knee-replacement surgery is far more arduous. Patients with a severely damaged meniscus may be eligible for a transplant from a cadaver. But the supply is limited, and there is risk of infection.
Researchers have tried for decades to come up with substitute materials that are as durable and flexible as a natural meniscus, and safe inside the body. Variants of Teflon, Dacron, nylon, silk and a variety of polyesters have all been tried, mostly in rabbits. But many shifted in place or haven’t been able to pass a key test: protecting the cartilage on the ends of the bones from further damage.
The NUsurface implant, made of medical-grade polymers, is the first synthetic substitute meniscus to progress to human trials. It is inserted with a small incision, and early studies show it progressively takes the shape of the patient’s knee contour. To date, it has been used in about 150 patients, mostly in Europe and Israel, according to the manufacturer, Active Implants Inc., of Memphis, Tenn.
The clinical trial in the U.S. aims to enroll at least 64 patients at seven medical centers, with half the participants receiving the implant and the rest receiving standard, nonsurgical treatment such as physical therapy and anti-inflammatory medication.
Mr. Ross, who was featured on local TV newscasts after receiving the implant, is an avid runner and martial-arts enthusiast. He was still in pain after having meniscus surgery on both knees in 2013. In January, he had a tear in his right knee repaired again and received the NUsurface implant in the left. He says the right knee healed faster than the left knee, which was swollen for days. He had physical therapy four days a week for three months and is now back to many of his activities. He hopes to be cleared to resume running and martial arts soon.
Despite the long recovery, Mr. Ross says he would have the implant surgery again. “Absolutely. Down the road, I know my left knee will wear much better than the right one,” he says.
Christopher Kaeding, the orthopedic surgeon at Ohio State University Wexner Medical Center who performed the surgery on Mr. Ross, say many of his patients would like to try the implant but their arthritis is too advanced for a good connection to form. Instead, it is aimed at preventing arthritis from setting in. “Hopefully it will fill a gap in our treatment spectrum,” Dr. Kaeding says.
Even if NUsurface wins Food and Drug Administration approval, it isn’t clear how long the implant will last. So far, the longest it has been in place is seven years. “If we get to a decade, we’ll be thrilled,” says Henry Klyce, chief executive of Active Implants. The company hasn’t decided how it will price the product.
The research under way at Cornell and Columbia takes a different approach—coaxing the body’s own stem cells to regenerate a natural meniscus.
The process starts with an MRI of the patient’s undamaged knee to measure the meniscus size and shape. The data is sent to a 3-D printer, which creates a precise replica of the meniscus out of biodegradable material like that used in surgical stitches. Researchers then infuse that scaffolding with two kinds of growth-factor proteins that attract stem cells once the device is implanted in the knee.
The precise order of growth proteins is critical to coaxing the stem cells to regrow a working meniscus, rather than scar tissue, as the scaffold is resorbed, says Jeremy Mao,director of tissue engineering at Columbia and lead researcher on the project.
Tests on the first group of sheep, which have knee joints similar to those in people, found that after three months the implant had structural and mechanical properties similar to a natural meniscus. The research was published in the journal Science Translational Medicine in December.
“We’re cautiously optimistic,” says Scott Rodeo, an orthopedic surgeon from the Hospital for Special Surgery in New York, who performed the sheep surgery. “Based on our preliminary analysis, this does support tissue formation.”
Researchers are now evaluating data from a second group of sheep, after six months with the regrown menisci. A third group was operated on in April, and will be assessed after one year. Dr. Mao is seeking funding to try the technique in humans as well.
Other meniscus replacement methods are in use in Europe, and researchers in the U.S. are experimenting with other scaffolding materials.
“The chances are, in the next two years, there will be multiple new approaches,” says Dr. Mao. “There’s no question the patients are out there.”