A Biologic Joint Replacement Strategy to Treat Patients with Severe Knee Trauma and Posttraumatic Knee Osteoarthritis

Principal Investigator: STANNARD, JAMES P
Program: PRORP
Proposal Number: OR140148
Award Number: W81XWH-15-1-0567
Funding Mechanism: Translational Research Award
Partnering Awards:
Award Amount: $1,086,472.00


Significant damage to the knee from athletic activities, military training, blunt trauma, or penetrating trauma inevitably leads to dysfunction, pain, and post-traumatic osteoarthritis (PTOA) and is the most common unfitting condition in medically retired military personnel. As identified in the most recent Extremity War Injuries (EWI) symposium, PTOA accounts for more than $3 billion in aggregate financial costs. Additionally, this symposium identified that "94.4% of the osteoarthritis (OA) can be attributed to combat injury," but fell short of identifying effective treatments other than joint replacement once OA develops. Cross et al. ranked degenerative arthritis with the third highest impact factor and the "most common unfitting condition" in their 2011 study of long-term disabilities in military personnel. Damaged knees rarely demonstrate substantive functional healing. Current practices in orthopaedic surgery attempt to limit the incidence and severity of joint deterioration, but despite recent advances and state-of-the-art treatment protocols, trauma to the joints can be associated with as high as a 65% incidence of debilitating OA. The fundamental problem driving this high rate of OA is the relative inability of articular cartilage to functionally heal. Risk factors that significantly influence the incidence and severity of OA after joint injury include the patient's age, extent of injury, and type and timing of treatments. Ideally, biologic "regenerative" treatments performed prior to the onset of debilitating OA would be used in these patients to prevent, or at least minimize, joint deterioration and dysfunction. However, regenerative strategies in orthopaedic trauma are not well developed, and therefore, a salvage procedure such as a total joint replacement is often necessary. While joint replacement with metallic and plastic implants generally succeeds in decreasing joint pain and improving limb function, the limited lifespan of implants, associated morbidity and complications are significant concerns. Perhaps more importantly, patients with total knee replacements cannot return to athletic activities, high-demand physical labor, or active military duty. Buckwalter and Lohmander have stated that "no currently available synthetic material or combination of materials duplicates the ability of articular cartilage to provide a painless, low-friction gliding surface and to distribute loads across a synovial joint."

Therefore, our solution is to use novel articular tissue transplantation strategies to functionally rebuild damaged knees. This will avoid the limitations of plastic and metallic implants while restoring full use of the limb for patients. Specifically, we have developed three allografting techniques that allow us to replace damaged cartilage, meniscus, and bone with viable tissues that can integrate and function at high levels. Our approach allows us to preserve organ donor tissues at the highest level of quality for more than twice as long as current technology, replace entire joint surfaces with "young" cartilage, and replace the entire meniscus with a viable, healthy meniscus. Importantly, all of these techniques have been validated in our translational canine model and used to treat clinical canine patients at our veterinary medical teaching hospital. This biologic joint replacement strategy has proven successful in restoring native joint structure and function such that working and performance dogs have returned to full athletic function while further degradation of the joint has been avoided for up to 6 years after surgery.

This proposal stems from the critical clinical need for more optimal treatment options for the millions of young to middle-aged, active military patients with damaged knees, including active duty and Veteran populations who have demonstrated a risk of injury at a level 10 times that of the civilian population. Our team, comprised of clinicians and basic scientists, has developed methods to address the current limitations in restoring these patients to high-level function. We subscribe to the "joint as an organ" philosophy and have used this philosophy to develop biologic solutions to articular disorders through a collaborative and comparative translational approach. The proposed research will allow us to move these solutions further forward in successfully treating traumatic joint injury in Soldiers and civilians, while also benefitting their four-legged companions.