What if injured joints could heal themselves before they develop osteoarthritis (OA)? Dr. James Martin’s current 3-year Arthritis Foundation-funded project, “Engineering Endogenous Cartilage Repair,” is trying to do just that- find ways to help joints heal before developing OA.
Dr. Martin and his team use special goats that have defects in areas of the thigh bones and cartilage, just above the knee. This closely mimics knee injuries that are seen in humans. The defects are surgically repaired with a hydrogel matrix that contains two important ingredients: repair cell attractant and growth factor. The repair cell attractant causes repair cells, called chondrogenic progenitor cells (CPCs), to migrate into the hydrogel. CPCs naturally occur in the cartilage. The growth factor, which is time-released over 10 days, causes the CPCs in the hydrogel to multiply and repair the injury with new cartilage.
After surgery, the goats are sent to the University of Iowa to heal. Their activity is restricted for 30 days in pens. Then they are allowed to return to pasture, where they spend most of the duration of the study. The injuries are examined with MRI imaging at one and three months. At six months, tissue samples are examined and measurements are made to determine how much healing occurred.
Dr. Martin and his team will begin analyzing the cartilage repair data this summer. The location of the injury – weight bearing areas vs non-weight bearing areas – will be an important part of the analyses. “We were expecting that a weight bearing joint would not respond as well as a non-weight bearing joint,” Dr. Martin explained. “However, cell culture experiments are showing that the pressure in a weight bearing joint may be beneficial to the healing process.”
OA is such a widespread and degenerative disease, affecting more than 30 million Americans, which is one of the reasons why Dr. Martin is studying it. He is particularly interested in post-traumatic OA (PTOA) because you know when an injury occurs and how severe the injury is. The Department of Defense (DOD) has expressed interest in his work to help treat veterans who are susceptible to PTOA because of battle or service-related injuries. “This is very exciting because it may offer a way for young people to avoid years of pain and eventual joint replacement surgeries,” Dr. Martin explained.
Dr. Martin would like to continue his work with advanced OA. “One of the problems with OA in older patients is that we don’t know when it starts, so it develops over decades. While the project I am currently working on should potentially work well in younger patients, it may work differently in a more advanced case of OA. We may need a different approach to jump start the CPCs that are present in an older injury. We may need additional ways to help begin the healing process,” he said.
Dr. Martin recently published an article on a study that laid some of the foundation for his current foundation-funded project. The article, Enhanced phagocytic capacity endows chondrogenic progenitor cells with a novel scavenger function within injured cartilage, looked at the role of CPCs in the cartilage healing process. He was awarded a patent and filed for a second patent on the technology related to his work with the hydrogel matrix and methods used for cartilage repair.
Dr. Martin is an associate professor at the University of Iowa. He works in the Department of Orthopedics and Rehabilitation, and the Department of Pharmaceutical Sciences and Experimental Therapeutics at the university. This is his first Arthritis Foundation funded project.