Doctors have long said cartilage can’t regenerate. They're now rethinking that.

Cartilage rarely gets attention—until it begins to fail.

For decades, arthritis patients have heard the same verdict: When cartilage wears away, it does not grow back. Unlike many tissues in the body, cartilage has little blood supply, which limits its ability to repair itself after injury. That biological limitation helps explain why osteoarthritis— caused by the gradual breakdown of cartilage—affects one in five adults in the United States and remains a leading cause of disability worldwide.

With no approved drug able to slow or reverse the disease, treatment typically focuses on managing pain and maintaining mobility through physical therapy. When damage becomes severe, the remaining option is often joint replacement surgery. The prevailing assumption has been that cartilage loss is inevitable, a mechanical consequence of lengthening lifespans.

Now scientists are beginning to challenge that assumption. Instead of only cushioning damage or replacing joints, they are exploring whether cartilage can be coaxed to repair itself.

A scaffold designed to rebuild cartilage

One approach focuses on rebuilding cartilage from the ground up.

“Motion is a fingerprint. It’s a marker of life,” says Samuel Stupp, a chemist and material scientist at Northwestern University. “If we’re not able to move without pain, it’s hard to be whole.”

Stupp’s research is built around the idea that restoring cartilage’s structure can help trigger its regeneration.

His team has designed an injectable material meant not only to replace what has been lost, but to create conditions that encourage new cartilage to grow. The scaffold, made from short protein fragments and a modified form of hyaluronic acid, is delivered directly into damaged areas of the joint.

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Once there, it assembles itself into tiny fibers that weave together into a soft but resilient mesh. The structure closely resembles healthy cartilage and, just as importantly, provides signals that guide surrounding cells toward building new tissue rather than forming scar‑like repair.

To see how the material performs under real‑world stress, the researchers tested it in sheep, whose knee joints resemble those of humans in size and the forces they endure. Over six months, joints treated with the scaffold began forming new cartilage rich in collagen II and proteoglycans, the molecules that give healthy cartilage its strength and flexibility. The repaired tissue looked and behaved more like native cartilage than the weaker fibrocartilage that often forms after standard treatments such as microfracture surgery, pointing to a repair that could last.

How aging changes cartilage’s ability to repair itself

But rebuilding cartilage’s structure is only one piece of the puzzle. Aging itself can make joints less capable of repair. At Stanford University, researchers are turning their attention to the biology of aging and the molecular changes that make cartilage less capable of repair.

Helen Blau, a professor of microbiology and immunology at Stanford, discovered—and continues to study—a protein called 15‑PGDH that rises steadily with age. The enzyme breaks down a key molecule essential to tissue repair, slowing regeneration and causing tissue to lose function. These proteins are referred to as “gerozymes,” molecular regulators that shape the biology of aging.

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Blau and her colleague, Nidhi Bhutani, an associate professor of orthopedic surgery, discovered that in older mice, blocking 15‑PGDH reversed the cartilage loss that normally accompanies aging in the knee. In animals with injuries resembling ACL tears, the treatment prevented osteoarthritis from taking hold. Treated mice moved more normally and put more weight on their injured limbs, a sign that their joints were functioning better.

Human tissue echoed those findings. Cartilage samples taken from knee replacement surgeries responded to the inhibitor in the lab by producing new, functional hyaline cartilage, the smooth, resilient tissue that allows joints to glide.

“People with joint pain are desperate to find relief, and they have very limited options,” says Blau. Bhutani adds, “This new inhibitor can address the root cause of pain by repairing the damage to the cartilage.”

Stopping the inflammation that destroys joints

Aging can slowly erode cartilage, but inflammation can destroy it quickly. At the Mayo Clinic, Christopher Evans, a professor of orthopedic surgery and molecular medicine, is focused less on regrowing cartilage, but on tackling the inflammatory signals that drive the disease itself.

“If we can stop the cycle of inflammation, we can preserve the joint before it fails,” says Evans.

Evans has spent decades studying interleukin‑1, a protein that helps the body respond to injury. In healthy tissue, its role is brief. In osteoarthritis, it lingers, fueling inflammation and accelerating cartilage breakdown. Blocking it with injected drugs has proven difficult because proteins introduced into a joint are quickly washed away through blood vessels and the lymphatic system.

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Gene therapy offered a way around that problem. Evans and his colleagues delivered genetic instructions directly into the knee, prompting joint cells to produce their own supply of a natural anti‑inflammatory protein. After a single injection, the joint became its own source of treatment, maintaining local levels of the protective molecule rather than losing it within hours.

In an early safety trial, levels of the protein remained elevated in joint fluid for at least a year, with no serious side effects linked to the therapy. Participants reported less pain and improved function, though the study was small and not designed to measure long‑term outcomes. Larger trials are now underway. The aim is not to rebuild cartilage outright, but to interrupt the inflammatory cycle that hastens its loss and preserve the joint before it fails.

None of these strategies has yet proven durable in large human trials. But together they reflect a shift in how scientists think about osteoarthritis. Long framed as inevitable wear and tear, the disease is increasingly understood as living biology, shaped by molecules, cells, and structure that may yet respond to intervention.