Researchers with Jefferson Orthopedics are using their experience and expertise in post-traumatic joint stiffness to develop treatments that could aid in optimal recovery and restoration of joint function for members of the military who sustain traumatic combat or combat-related injuries.
Their proposal, "Prevention of the Post-Traumatic Fibrotic Response in Joints," recently won a three-year, $1 million dollar grant from Department of Defense (DoD), the largest of three grants awarded in this category nationwide.
A number of studies done on a population of active duty members of the United States Military Service suggest that post-traumatic joint injuries and associated joint stiffness not only limit the range of motion (ROM) but also constitute the major risk factors in developing osteoarthritis. The DoD 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, 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, Ph.D., 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," says Dr. Fertala, Principal Investigator on the study along with Joseph Abboud, M.D., shoulder surgeon with the Rothman Institute at Jefferson and Pedro Beredjiklian, M.D., 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 ROM of analyzed 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-bed transition of the proposed therapeutic route.
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.
Source: Thomas Jefferson University