New Flexible Hydrogel Could Improve Drug Delivery for Post-Traumatic Osteoarthritis Treatment

Mass General Brigham researchers have developed a new hydrogel that did not break down under repeated joint stress and resulted in long-lasting, sustained drug release in preclinical studies.

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, Perioperative and Pain Medicine at Brigham and Women’s Hospital, 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,” said co-senior author Joerg Ermann, MD, an attending rheumatologist in the Division of Rheumatology, Inflammation and Immunity at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School. “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.”

Authorship: In addition to Karp, Joshi, and Ermann, other Mass General Brigham authors include Jing Yan, Mickael Dang, Kai Slaughter, Yufeng Wang, Dana Wu, Trevor Ung, Nutan Bhingaradiya, Virja Pandya, Mu Xian Chen, Shahdeep Kaur, Sachin Bhagchandani, John Joseph, Jingjing Gao, Mahima Dewani, Rachel Chun Wai Chu, Ryan Chak Sang Yip, Eli Weldon, Purna Shah, Nishkal Dhiraj Pisal, Chetan Shukla, Nicholas Sherman, James Luo, and Thomas Conway.

Disclosures: Joshi, Karp, Slaughter, Bhagchandani and Sherman have pending and issued patents on the hydrogel platform described in this manuscript. The authors declare that they have no other competing interests.

Funding: This work was supported by grants from the National Institutes of Health (R01AR077718), Department of Defense (W81XWH-14-1-0229), Rheumatology Research Foundation, King Abdulaziz City for Science and Technology through the Center of Excellence for Biomedicine, and the Football Players Health Study grant, which is funded by the National Football League Players Association.

Paper cited: Joshi, N et al. “A Mechanically Resilient Soft Hydrogel Improves Drug Delivery for Treating Post-Traumatic Osteoarthritis in Physically Active Joints” Proceedings of the National Academy of Sciences of the United States of America DOI: 10.1073/pnas.2409729122