Peripheral nerve reconstruction: NO hope for advanced regeneration

外伤性周围神经损伤（PNI）是常见的，主要影响上肢的年轻经济活动的成年人，男女。PNI给患者和整个社会带来了严重的经济后果，尽管有现代显微外科技术，功能恢复总是不完整的。对患者来说，结果是手部感觉受损，运动功能下降，疼痛和寒冷耐受；此外，这些症状的持久性往往导致心理疾病和终身福祉受损。最大的重建挑战在于大约1 / 5的PNI患者存在“神经间隙”（即由创伤引起的神经缺损），无法直接修复两个神经残端。神经间隙可以用自体神经移植来重建，这种方法牺牲了下肢部分的感觉功能，以恢复手部的关键功能。神经移植术后预后较差，且随着间隙距离的增加而恶化。我们开发了一种聚合物神经修复装置“Polynerve”，它具有简单易于升级的制造方法；通过在导管的内腔上植入凹槽，它试图解决PNI后许旺细胞引导再生的生物学问题。我们已经在曼彻斯特完成了一期临床试验，在治疗小神经间隙损伤方面取得了很好的效果。现在，我们试图增强损伤部位的生物反应，以促进再生。一氧化氮（NO）是一种有效的自由基，可能通过巨噬细胞相互作用调节参与神经元和血管再生的多种生物过程。已知巨噬细胞诱导的新血管形成导致雪旺细胞介导的周围神经再生；因此，NO是增强PNI再生的潜在干预手段。

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.