Hydrogel Relieves Pain and Repairs Cartilage in Osteoarthritis

For millions of people living with osteoarthritis, daily life can involve a frustrating cycle of pain and stiffness. While current treatments like over-the-counter medications or steroid injections can temporarily dull the ache, they do not stop the joint from deteriorating.

A Yale study published in the journal Bioactive Materials found that the medication lacosamide acts as a highly effective, dual-purpose treatment that relieves joint pain and reverses cartilage damage in osteoarthritis, especially when a specialized hydrogel delivers the drug directly into the joint.

Osteoarthritis is commonly described as a wear-and-tear condition, but the phrase oversimplifies the complex biological process that scientists are working to better understand.

Inside the joint, specialized cells called chondrocytes are constantly balancing two opposing tasks: building new cartilage and breaking down old tissue. This delicate balance is disrupted when osteoarthritis is present. Destructive forces begin to take over, and cartilage loss speeds up until bones begin to rub against each other. Over time, this progression can create the need for joint reconstruction surgery such as a total knee replacement.

"There is a major unmet need in osteoarthritis," says the study’s principal investigator and Charles W. Ohse Professor of Orthopaedics & Rehabilitation, Chuan-Ju Liu, PhD. "We need therapies that don’t just mask pain but actually change how the disease progresses."

There is currently no U.S. Food and Drug Administration-approved medicine that can both halt this pain and prevent the structural cartilage from breaking down. However, a new study led by Liu points to a different strategy that could both protect joint tissue and reduce pain at the same time.

By repurposing an existing medication and delivering it through a high-tech smart gel, researchers have discovered a way to potentially protect joints and provide long-lasting relief without the need for addictive opioids.

Liu’s research centers on a specific protein called Nav1.7, which functions as a sodium channel. Sodium channels act like microscopic gates on cell membranes, helping cells transmit electrical signals.

For years, scientists believed Nav1.7 existed mainly in the specialized nerve cells that send pain signals to the brain. Liu’s recent discoveries revealed that this same channel is also very active inside the cartilage-maintaining chondrocytes.

In a healthy joint, Nav1.7 stays relatively quiet. But in a joint afflicted with osteoarthritis, it becomes overactive. This overactivity acts like a volume knob turned up too high, not only increasing pain signaling but also triggering the chondrocytes to start destroying the very cartilage they are supposed to protect. This finding changes how researchers view osteoarthritis, revealing Nav1.7 as a rare, dual-purpose target that influences both pain perception and tissue health.

"When Nav1.7 becomes dysregulated, it contributes to both joint degeneration and pain," Liu says. "Our findings suggest that Nav1.7 is a dual-acting target. By blocking this single protein, we can potentially quiet the pain nerves and tell the cartilage cells to not only stop breaking down but start repairing as well."

Rather than developing a new drug, Liu’s team evaluated existing sodium channel inhibitors. Lacosamide produced strong biological effects at much lower concentrations, and it had a better safety profile compared to older medications in its class.

During lab experiments, Liu and his researchers noticed an interesting phenomenon: Lacosamide dosing did not follow a simple more-is-better rule. At an ideal, low concentration, it worked perfectly to encourage cells to make cartilage-building proteins while stopping tissue breakdown. However, if the dose was too high or too low, the medical benefit began to disappear.

"This tells us the system is finely tuned," Liu notes. "There is an optimal range where the drug helps restore balance without overcorrecting. What stood out was not just its effectiveness, but how little of a dose was needed."

When the researchers looked closer at how lacosamide protects the joint, they discovered it influences cellular communication by triggering the release of two helpful signaling proteins: HSP70 and midkine. These molecules act as internal bodyguards for the joint. HSP70 helps cells recover from stress and promotes tissue repair, while midkine helps control inflammation and protect joint tissues from degenerating.

"These proteins create a supportive environment for cartilage maintenance," Liu explains. "They allow the effects of the drug to extend beyond individual cells and influence the entire tissue."

While oral medications proved to be effective in preclinical trials, they circulate throughout the entire body and can cause unwanted side effects. To avoid this, the researchers explored intra-articular injection, delivering the drug by needle directly into the joint.

However, a major hurdle remained. “The knee joint, which is also the most common location for osteoarthritis, naturally acts like a leaky bucket,” Liu says. “The body's drainage system can clear out liquids injected into the knee within hours.”

To overcome this limitation, Liu’s team developed a specialized hydrogel made from Collagen II. This material is thermoresponsive, meaning it stays liquid in a cool syringe but solidifies into a sturdy, jelly-like substance once it hits the warmth of the body. This smart gel keeps the medicine concentrated exactly where it is needed, slowly dripping the drug out over several weeks.

"The hydrogel acts as a local reservoir," Liu says. "It holds the drug in place in the location it is needed most and releases it slowly over time. It transforms a daily pill into a long-lasting, local treatment that stays active for a month or longer."

In the same preclinical trials, a single injection of the lacosamide-loaded gel every four weeks was more effective at preventing cartilage loss than a daily oral pill.

Because lacosamide is already approved for human use, the path toward clinical testing in osteoarthritis patients may be much faster than creating something entirely new.

Furthermore, lacosamide has already been shown in human trials to help patients with specific nerve-related pain disorders caused by Nav1.7 mutations, providing researchers with high confidence that these laboratory findings will translate to real-world human relief.

This study additionally highlights a broader shift in medical research, combining pharmacology with advanced biomaterials to change how treatments are delivered. For patients, this could eventually mean fewer medical procedures, minimal side effects, and long-lasting structural protection.

"We are not just developing a treatment," Liu concludes. "We are developing a system that allows the medicine to work more effectively where it matters most. Our goal is to move beyond symptom control and towards true disease modification. This effort brings us closer to that reality."