As protective body armor has advanced, the number of combat-related deaths has steadily decreased, but the severity of wounds sustained to the regions that are not protected by body armor, such as the limbs, has greatly increased and now accounts for over half of all such injuries. When injuries to the limbs affect the joints, such as the knees, the body is often unable to heal itself and progresses into a deteriorating condition coined post-traumatic osteoarthritis (PTOA), which can and often does result in continual pain and failure of the joint. It is of significant interest, therefore, to develop new treatments that are capable of intervening in this process such that joint deterioration is slowed and the joint tissues are allowed to heal. Given there are multiple processes that contribute to this joint deterioration, it is crucial that a comprehensive approach be taken so as to combat the disease on all fronts. One way to do this is to simultaneously treat the inflammation that accompanies the injury and complicates the wound healing process while delivering agents that promote regeneration of the damage tissue. While there are a number of ways to accomplish these goals, the co-administration of highly potent drugs that can combat the disease in a highly specific manner represents a desirable solution as it offers a simplistic and reliable treatment plan.

Thus, the overall goal of the proposed study is to evaluate the ability of two drugs, one an anti-inflammatory drug (Anakinra) and the other a new regenerative agent (KA-9) specifically designed to promote healing of the injured cartilage, to: (1) prevent further breakdown of the joint and (2) restore the ability of the joint to move and function properly. We believe the combination of these drugs will result in improved joint structure and function following traumatic injury relative to both untreated injuries and injuries treated with a clinical therapy derived from the blood. We will pursue this goal by first assessing the ability of the anti-inflammatory drug (Anakinra) to control the inflammation within the joint space in the time period immediately following injury and subsequently evaluate regenerative and functional outcomes associated with the treatment. Throughout these studies, we will measure how well the joints are healing by examining the cells, tissues, and fluids within the joints for molecular indications of improvement and assess the structure and function of the joint through the use of imaging and observing how there joints move as they walk.

Each of the treatments discussed herein were carefully selected for their potential to work together to promote healing and to be put into use for the treatment of injured people in the near future. As such, this study represents a significant scientific advancement with the potential to transform the care and quality of life of our wounded Service members.