Hydrogel-based drug delivery offers hope for post-traumatic osteoarthritis

Post-traumatic osteoarthritis (PTOA) is a condition that affects joints after an injury. Current treatments focus on relieving symptoms but do not prevent or stop the progression of the condition. Although emerging therapies have shown promise in preclinical studies, a major obstacle is delivering these therapies effectively into the joint, a highly dynamic environment subjected to constant mechanical stress. Researchers at Mass General Brigham have created a new hydrogel to improve drug delivery for treating PTOA. The hydrogel, which is designed to offer sustained drug release even during continuous joint movement, showed promising results in preclinical studies that mimicked the joint stress of running, highlighting the hydrogel's potential for treating PTOA in physically active patients. Results are published in Proceedings of the National Academy of Sciences of the United States of America (PNAS).

"Disease-modifying drugs could slow, halt, or reverse PTOA, but rapid drug clearance from joints limits their effectiveness. Hydrogels can extend drug release, but can break down under mechanical stress, such as from exercise," said lead and co-senior author Nitin Joshi, PhD, associate bioengineer in the Department of Anesthesiology, Peripoperative and Pain Medicine at Brigham and Women's Hospital (BWH), a founding member of the Mass General Brigham healthcare system. Joshi is also an assistant professor of anesthesia at Harvard Medical School.

"We recognized these limitations and designed a hydrogel that continuously releases medication without being affected by mechanical stress" said co-senior author Jeffrey Karp, PhD, distinguished chair of anesthesiology at BWH. Karp is also a professor of anesthesia at HMS.

For the study, which was funded by the National Institutes of Health, researchers used triglycerol monostearate (TG-18), a common food additive, to create a hydrogel that rapidly repairs itself after mechanical stress. In a mouse model, they found that the hydrogel was self-healing, meaning it liquefied under mechanical stress and then instantly reformed. This self-healing property ensured long-lasting, stable and sustained release of a disease-modifying drug-even during continuous joint movement-and significantly reduced cartilage damage. Interestingly, the hydrogel also improved joint lubrication.

Our hydrogel technology could transform the treatment of PTOA by reducing the need for frequent injections, slowing disease progression, and potentially delaying or preventing surgery. This is particularly important for athletes, military personnel, and young adults recovering from joint injuries who need effective therapies that allow them to maintain active lifestyles."

Joerg Ermann, MD, co-senior author, attending rheumatologist in the Division of Rheumatology, Inflammation and Immunity at BWH and assistant professor of medicine at Harvard Medical School