Armed with a three-year, $1 million grant from the U.S. Department of Defense, physician-researchers at Jefferson Orthopedics are using their experience and expertise in joint health to develop treatments for members of the military who sustain traumatic combat or combat-related injuries.
The federal grant – the largest of three grants awarded in this category nationwide – funds the Jefferson proposal entitled “Prevention of the Post-Traumatic Fibrotic Response in Joints.”
A number of studies done on active duty members of the military suggest that post-traumatic joint injuries and associated joint stiffness not only limit the range of motion but also constitute the major risk factors in developing osteoarthritis.
The Department of Defense sought the expertise of the medical community to look into the problem.
Following a traumatic injury, the tissue in the affected area produces collagen-rich deposits or fibrils as it heals. These can appear on the surface of the skin as scars. In severe trauma of joints, however, the body is prone to excessive production of these collagen-rich fibrotic deposits in the joint tissues, leading to localized fibrosis and joint stiffness.
In 2008, Jefferson researcher Andrzej Fertala, PhD, and colleagues discovered an antibody that curtailed the production of collagen fibrils after trauma.
“The production of collagen fibrils following joint injury is like the building of a brick wall inside and around the joint structure,” explains Fertala. “Our antibody binds to the collagen molecules before they incorporate into fibrils and prevents prolonged building, prohibiting or limiting the formation of this rigid fibrotic structure before a dense wall can form.”
Dr. Fertala is a principal investigator on the study along with Joseph Abboud, MD, shoulder surgeon with the Rothman Institute at Jefferson and Pedro Beredjiklian, M.D., an orthopedic hand surgeon with the Rothman Institute.
This pre-clinical study will analyze the effectiveness of the antibody in models that mimic post-traumatic joint stiffness. The models will post-operatively receive the antibody and will then be evaluated for its effectiveness through the measurements of collagen content and range of motion of the joints. Appropriate controls, which include a group treated with control antibody and a group treated with an anti-inflammatory agent, will be also employed.
The union of clinical and basic research partners ensures an efficient execution and forms a starting base for a bench-to-bedside transition of the proposed therapeutic route to turn results into clinical application for military personnel and others who suffer traumatic joint injuries.
The long-range objective is to apply this novel approach to reduce the joint stiffness-associated fibrosis that will help maintain the correct range of motion following joint trauma and also prevent a long-term risk of developing osteoarthritis for the men and women of the military who sustain traumatic combat and combat-related injuries during their service.