The obvious alternative is an intra-articular injection—delivering the drug directly into the knee or hip. However, the human joint is not a sealed container. "The knee joint, which is also the most common location for osteoarthritis, naturally acts like a leaky bucket," Liu explains. "The body’s drainage system can clear out liquids injected into the knee within hours."
To solve this, the researchers developed a "smart" hydrogel made from Collagen II, the primary protein found in cartilage. This hydrogel is engineered to be thermosensitive. It remains a thin liquid while inside a cool syringe, allowing for easy injection through a standard needle. However, once it enters the joint and reaches the body’s natural temperature, it undergoes a phase change, transforming into a firm, jelly-like reservoir.
This gel traps the lacosamide within the joint space, preventing it from being washed away by the lymphatic system. Instead of the drug disappearing in hours, the hydrogel allows for a slow, sustained release of the medication over several weeks.
"The hydrogel acts as a local reservoir," says Liu. "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 preclinical trials, the results were definitive. A single injection of the lacosamide-loaded gel every four weeks was found to be significantly more effective at preventing cartilage loss than a daily oral dose of the medication. This sustained-release approach ensured the drug remained within the "Goldilocks" concentration range required for tissue regeneration.
Existing Drug Could Speed Clinical Testing
The fact that lacosamide is already FDA-approved for epilepsy provides a major advantage for the future of this research. Because the safety profile of the drug is well-documented in humans, the path toward clinical trials for osteoarthritis may be significantly shorter than it would be for an experimental compound.
Furthermore, lacosamide has already been studied in humans for certain rare nerve pain conditions caused by genetic mutations in the Nav1.7 protein. These existing human data points provide the Yale team with a high degree of confidence that the dual-action effects observed in the lab will translate effectively to human patients.
Beyond the immediate potential of lacosamide, this study represents a broader trend in "precision orthopaedics"—a field that combines traditional pharmacology with advanced biomaterials to control the delivery of medicine with surgical precision. By focusing on disease modification rather than just symptom management, the Yale researchers are aiming for a future where osteoarthritis is no longer a slow march toward surgery, but a manageable condition where the joint is empowered to heal itself.
"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."
