Large Extremity Peripheral Nerve Repair in Nonhuman Primate Models
Abstract
The overall goal of this proposal is to develop a novel technology to produce improved recovery for wounded Warfighters that suffer from severe nerve damage in the arms caused by combat trauma. Use of improvised explosive devices (IED) by enemy fighters has led to extensive traumatic injuries to the limbs, typically involving lower limb amputation and a high proportion of peripheral nerve damage associated with trauma to the upper limbs, causing pain, paralysis, or limb malfunction. IED blast or projectile injury destroys tissue and a loss of a segment of nerve must be repaired for any hope of nerve regeneration and recovery of function in the hand to occur. Nerve loss is considerable in the wounded Warfighter, with gaps of 4-8 cm being typical. The standard of care for repair of such an injury in civilian medicine is autologous graft, where a segment of a sensory nerve, such as the sural nerve in the leg, is taken and sutured across the gap to bring the nerve back into continuity. The regenerating nerves then have an opportunity to reach the target muscles, and function can be recovered to a certain extent. However, due to the severity of other injuries to the wounded Warfighter, including limb amputation(s), a suitable donor nerve may not be available and, even if available, may not be risked in a complex wound where there is a high risk of infection and other complications. In such wounded Warfighters, processed allograft products are currently the best alternative. These grafts are prepared from human cadaveric tissue by a process that leaves the nerve architecture intact to act as a guide for regenerating nerves once the graft has been sewn in place. Even under the best of conditions, the functional recovery that is obtained using current surgical methods is poor using these products. In wounded Warfighters that experience devastating injuries including loss of limb(s), it is vitally important, for the patient s long-term quality of life and possible return to active duty, that some function can be recovered in the remaining limbs. There is a pressing need for a new method to improve functional recovery by minimizing some of the factors that inhibit nerve regeneration in the allograft. Our technology provides an improved approach to peripheral nerve repair, using a light-activated dye and a biocompatible nerve wrap to effectively seal the nerve graft in place without using sutures. Suturing a nerve causes various problems that reduce nerve regeneration. Needle passage causes damage to the fragile nerve tissue and the suture material can also cause inflammation and scarring to block regenerating nerves. In our technology, the nerve graft is sealed in place by light-induced chemical bonding of a wrap material over the two sites of attachment of the graft to the nerve stumps. Importantly, this provides a better environment for the nerve to regenerate as the seal is water-tight and continuous and contains the nerve fibers and growth factors that promote regeneration within the nerve. The seal also prevents escape of the regenerating axons from the nerve itself and escaping axons not only reduce the extent of recovery of function but also cause severe pain through formation of a neuroma outside the normal protective nerve environment. We have demonstrated significant improvement of nerve regeneration in small animal models using our technology against standard suture repair for autologous graft repairs. We have also improved outcomes for allograft repair to the extent that no significant difference in outcomes is seen with respect to standard autologous graft repair using suture. We propose to move this approach to a nonhuman primate model that is much more relevant to the unique situations of nerve damage in wounded Warfighters to enable true functional testing of nerve recovery using allograft products to repair upper limb injury involving large nerve gaps. This is not possible in other large anim
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710059
Entities
People
- Robert W Redmond
Organizations
- Massachusetts General Hospital
- United States Army