Objectives and Rationale: Each year, thousands of Service members sustain battlefield injuries that involve damage to peripheral nerves, many of which affect sensation in and movement of the arms, legs, hands, and fingers. Nerves consist of bundles of axon fibers that connect the brain and spinal cord to the muscles of the body, where they play roles in our ability to feel and move. Typically, in peripheral nerve injuries, these axons are severed or crushed. Since axons only regenerate at a rate of about 1 millimeter per day, too much time is often necessary to achieve a return of normal sensation and or movement. In such prolonged cases of axon regeneration, functional and sensory outcomes often remain unsatisfactory. Amniotic membrane, derived from donated umbilical cords, can serve as a barrier between the regenerating nerves and the surrounding inflamed environment. Among other characteristics, amniotic membrane has been shown to be anti-inflammatory, which can aid in the process of nerve regeneration by preventing scar formation. When wrapped around a crushed nerve, an amniotic membrane can enhance regeneration speed and ultimately improve the amount of function recovered after the injury.

Applicability of the Research and Risks: The work in this application focuses on a potential treatment strategy to improve outcomes for individuals with nerve crush injuries, which may be sustained by Service members as a result of trauma on or off the battlefield. In addition, results of this study will provide a s model by which to study nerve crush injury, something that is currently lacking in this area. The technical risk associated with developing this model is related to identifying the optimal level of the parameters involved. Moreover, the tools used for developing the crush nerve injury model should be calibrated to ensure avoiding uncontrolled increase in surface pressure during applying compression on nerve, which could lead to complete nerve transection. Additionally, when this treatment is translated to humans, there is a risk that disease transmission or rejection by the recipient could occur. However, the amniotic membrane used in this study will be minimally processed to prevent rejection, and all donors are thoroughly screened for potential disease transmission risk by a medical director.

Timeline: We expect that during the 2 years of the funding period, we will establish and verify the optimal parameters for a reproducible animal model of nerve crush injury as well as provide evidence for increased regeneration with the use of an amniotic membrane wrap. Experimental evidence in improving outcomes after peripheral nerve injury is vital to the adoption of such a product by surgeons. The success of this study will drive use of amniotic membrane in clinical application and will provide improvements in quality of life for many people who experience these types of injuries.

Military Benefit: While the use of an amniotic membrane as a nerve wrap for peripheral nerve crush injuries will aid in the recovery of military and non-military personnel with a variety of nerve injuries, the endpoint is an increase in the percentage of Service members with these injuries who will be able to return to full military duty. Recovery of normal sensation and movement will lead to a reduction in long-term disability, which may reduce the high costs associated with these injuries and the dependence of these individuals on caregivers, many of whom are family members and friends of the Service member. Faster and more efficient recovery may reduce dependence on others for assistance with daily activities and may help them lead more normal lives after these typically devastating and life-altering injuries. Finally, since up to 5% of all trauma patients sustain nerve injuries and only 10% regain normal function, this research can potentially benefit many thousands of individuals.