Peripheral nerve reconstruction: NO hope for advanced regeneration

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Traumatic peripheral nerve injury (PNI) is common and mainly affects the upper limbs of young economically active adults, of both genders. PNI presents serious economic consequences for the patient, and society as a whole, and despite modern microsurgical techniques, functional restoration is always incomplete. For the patient, the outcome is impaired hand sensation, reduced motor function alongside pain and cold intolerance; furthermore, the enduring nature of these symptoms frequently results in psychosocial morbidity and a lifelong impairment of well-being. The greatest reconstructive challenge lies with the approximately 1 in 5 PNI patients with a 'nerve gap' (i.e. a nerve defect caused by the trauma) where direct repair of the two nerve stumps is not possible. Nerve gaps may be reconstructed using autologous nerve grafts, which sacrifice sensory function in parts of the lower limb in an effort to restore critical function in the hand. The outcomes following nerve grafting are poor and worsen with increasing gap distance.We have developed a polymer nerve repair device 'Polynerve' that has a simple easily upscalable manufacturing methodology; by incorporating grooves on the inner lumen of the conduit, it attempts to address the biology of the Schwann cell - guiding regeneration following PNI. We have completed Phase 1 clinical trials in Manchester with excellent outcomes on small nerve gap injuries.Now, we seek to augment the biological response at the site of injury to favour regeneration. Nitric Oxide (NO) is a potent free radical that regulates multiple biological processes with involvement in neuronal and vascular regeneration likely via macrophage interaction. It is known that macrophage-induced new blood vessel formation leads Schwann cell-mediated regeneration of peripheral nerves; thus, NO is a potential intervention to augment PNI regeneration.