Tracey Greene feels younger again, or at least his right knee does.
After years of hard-hitting physical activity, from football as a kid to martial arts not so long ago, that knee started to show signs of wear in 2023.
When he punched hard, it hurt. Doing squats hurt, too, as did taking the stairs. “My knee was on fire,” he says.
Greene, 52, was going through the kind of wear and tear that drives nearly 800,000 people to get a knee replaced in the United States each year. It’s a serious surgery taking many hours, followed by a long recovery. It’s only meant for those with disabling knee pain and extreme cartilage deterioration. Greene wasn’t there yet. So what were his options?
Why Wait for Knee Replacement?
When all the cartilage in the knee is gone and bone meets bone, knee replacement is the only effective fix. But if you're close, and doctors tell you that a knee replacement is all but inevitable, why not just bite the bullet and get the surgery early?
Because knee replacements don’t last forever. The new knee wears out after two or three decades, and then things get trickier, says Rachel Frank, MD, an orthopedic surgeon and associate professor of orthopedics at the University of Colorado School of Medicine.
To replace a knee, the surgeon must cut away bone, leaving less for a second procedure, Frank says. ”The results tend to get worse with each subsequent revision. And there's a lot of reasons for that, but in brief you have to resect a little bone each time you do it, and there's only so much bone you can resect,” she says. That’s why doctors tend to try to wait as long as possible to do the procedure.
Some of her most difficult conversations are with patients between 35 and 55 who’ve lost so much cartilage that bone meets bone, a demographic she refers to as “tweeners” because they are in between solutions. “They're too young for knee replacement, but if their knee is too far gone for me to do the [procedures] that I do, we don't have a ton of options other than injections,” Frank says.
Greene was lucky: His knee was in bad shape but not too bad for cartilage restoration.
This approach uses a variety of surgeries to repair or restore cartilage damaged by injury or worn away by normal wear and tear. Greene’s doctor had injected hyaluronic acid into his knee to relieve the pain, but that was only a temporary solution. Then, she recommended an implant called CartiHeal Agili-C that had recently been approved by the FDA. These porous plugs made from coral exoskeletons are the size of mini marshmallows and fit into holes the surgeon drills through cartilage into bone. Blood from the bone rises through the plugs to encourage cartilage growth.
Greene decided to do the surgery soon afterward. He says he healed quickly. He is running again, albeit on soft tracks or grass. And he’s back in the gym every morning doing free weights. But cartilage restoration doesn’t always work so well.
Cartilage restoration has been around for decades, but results, though improving, are still inconsistent, especially for those with advanced cartilage damage, called osteoarthritis.
“Every day in the clinic, I'm telling at least five or six people ‘Your knee is a tweener. … We can push the limits with the cartilage restoration, but you may go through a big surgery with a big recovery and not have a great result,” says Frank.
Types of Cartilage Restoration
J. Richard Steadman, MD, a longtime doctor for the U.S. Alpine Ski Team, developed a procedure called ‘microfracture’ in the 1980s. It taps bone marrow to regrow knee cartilage. He poked tiny holes in the underlying bone, which restored cartilage. But that new cartilage tended to be fibrous rather than the native smooth stuff in knees called “hyaline” cartilage. It broke down quickly.
Newer methods rely on gluing transplanted cartilage to the damaged site after scraping a thin layer of bone to induce blood flow. Sometimes, an entire “plug” of cartilage and underlying bone is extracted and implanted.
The tissue can come from a cadaver or from the patient – transplanted from another part of the knee or, in the case of cartilage without bone, biopsied and cultured in a lab before it’s put back in.
Some patients get two or three decades of use from transplanted cartilage, Frank says. But some get no benefit at all. "We don't fully understand why some patients get better and some patients don't," Frank says, adding that most get at least 10 to 15 years of relief.
Age is a factor when deciding on treatment, but Frank says there are no strict cutoffs.
For one thing, people age at different rates. Some in their 50s have knees that look like they're in their 30s, while some in their 30s have knees that look decades older, she says.
People over 50 typically have significant wear and tear on their knees, so a cartilage transplant might fix only part of the problem.
Younger knees are fresher, so transplants are generally more successful. But many of the patients she sees have already had multiple knee surgeries.
"Their knee is already significantly worn out, and it can be difficult to give them a good option even in their 20s," Frank says. "So age is a variable, but it's more complex than just age."
She’s practiced with CartiHeal Agili-C on cadavers and thinks it’s a promising new technology.
"The whole goal is for your body to take over where it's been put in, and ideally you get native bone and cartilage in that area,” she says. “It's been really successful in the initial trials."
But CartiHeal Agili-C is still a niche product (for more, see Side Bar: What We Know About CartiHeal Agili-C at end). Among the older approaches are:
Debridement: Cutting away cartilage that is damaged and separating from the bone to leave clean edges that are less likely to peel. It’s not very effective, but it’s the least invasive restoration procedure, taking all of 10 minutes in the operating room, says Adam Yanke, MD, PhD, a sports medicine surgeon with Midwest Orthopaedics at RUSH University Medical Center in Chicago.
Microfracture: poking holes in the bone beneath cartilage to encourage a flow of the blood into damaged cartilage. It’s low-risk but less durable – better than nothing, Frank says. It produces a large proportion of fibrocartilage, fibrous stuff that tends to break down after a couple of years. It’s less effective than newer techniques that produce more hyaline cartilage like the native smooth and durable stuff in knees, Frank says. Yanke says it’s largely fallen by the wayside, with only “pockets” of surgeons doing it these days.
Implantation: Transplanting cartilage from a cadaver; transplanting it from another part of the patient’s knee; or harvesting it from the patient’s knee with a biopsy, then growing the tissue in a lab and implanting it (matrix-induced autologous chondrocyte implantation, or MACI). Surgeons used to attach the transplanted cartilage with tiny sutures, but these days, they use fibrin glue, says Frank. They also scrape away a thin layer of underlying bone to get that healing blood flowing, she says.
Reconstruction: Transplanting cartilage and underlying bone, using tissue from a cadaver (technically, osteochondral allograft transfer) or from the patient (osteochondral autograft transfer, or OATS) that was extracted in the form of a plug. CartiHeal Agili-C is a new kind of artificial plug that shares some similarities with the older methods but brings something new to the table. Unlike the older methods, it’s not flesh that’s meant to integrate with the knee. Instead, it’s meant to dissolve after structurally supporting upwelling blood that creates new tissue.
Still, the consensus from the experts interviewed here is that there is no long-term solution for younger people with full blown arthritis (stage 4).
There may be more options in coming years. For instance, Frank, at the University of Colorado, will be taking part in a trial that uses stem cells from umbilical cord blood to treat knee cartilage damage. Yanke says there’s research into injectable substances that might break cycles of inflammation after surgery, though that’s probably more preventive than restorative. And Samuel Stupp, PhD, a chemist and materials scientist at Northwestern University, is working on a bioactive gel that tells cartilage cells to replicate.
Only time will tell if these products will bring more consistency to cartilage restoration outcomes.
Side Bar: What We Know About CartiHeal Agili-C
The device maker (currently Smith + Nephew) reported that 167 patients treated with its product in knee implants did twice as well two years after surgery as 84 others who got microfracture or removal of damaged cartilage, a procedure called “debridement.”
Outcomes for these 167 continued to look strong after four years, according to the company’s follow-up research published last year. Steven Moore, senior director of global marketing for the product at owner Smith + Nephew, says the five-year data, to be published in a study by June, continues to show promise.
Tracey Greene’s surgeon, Sabrina Strickland, MD, with the New York City-based Hospital for Special Surgery, is one of the most prolific users of CartiHeal Agili-C, according to Moore. The associate professor at Cornell University says only one of her roughly two dozen patients who got the treatment has had a less-than-positive outcome.
CartiHeal Agili-C is "a nice idea,” says Samuel Stupp, a chemist and materials scientist at Northwestern University. He says he hasn’t seen compelling evidence that Agili-C produces the high-quality smooth “hyaline” cartilage that grows in children’s knees or that it improves on other cartilage restoration methods currently in use. Stupp is researching a bioactive material that theoretically could make knees regenerate hyaline cartilage.
He says the CartiHeal Agili-C trial involved a relatively small sample of patients. “The statistics are not hugely significant yet,” he says. “In the cohort of patients that they looked at, it seemed to be better, slightly, in terms of pain reduction. Now, does that mean that you regenerated hyaline – perfect, ideal cartilage? No. Doesn't mean that.”
But there is some evidence that CartiHeal Agili-C implants encourage growth of the good knee cartilage. Researchers can’t pull new cartilage out of implant patients to inspect it, but a 2021 study observed significant hyaline cartilage formation in a patient whose cartilage was extracted during a knee replacement. Also, a 2015 study found significant amounts of new hyaline in goats implanted with the plugs.
This apparent success has led to some head-scratching.
“CartiHeal has kind of turned the cartilage restoration world a little bit on its head,” says Adam Yanke, MD, PhD, a sports medicine surgeon with Midwest Orthopaedics at RUSH University Medical Center. “The company has done a great job with their clinical trials, and the data that they present is very compelling. But the indications and the mechanism and the way that it works does fly in the face of how we've thought about cartilage transplantation to date.”
The surprise is in part because the product relies on blood rising from bone just as microfracture does, says the associate professor at RUSH. Also, when the plugs are burrowed into damaged tissue, they repair not only that tissue but also injured areas next to it, says Yanke, who implanted CartiHeal Agili-C in a patient for the first time in January.
