Murphy Ralph, Faroni Alessandro, Wong Jason, Reid Adam
Blond McIndoe Laboratories, Division of Cell Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, M13 9PT, UK.
Department of Plastic Surgery & Burns, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
F1000Res. 2019 Jun 24;8:959. doi: 10.12688/f1000research.19497.1. eCollection 2019.
Peripheral nerve injuries are common, with approximately 9,000 cases in the UK annually. Young working individuals are predominantly affected, leading to significant health and social implications. Functional recovery is often poor with impaired hand sensation, reduced motor function and pain and cold intolerance. Where a nerve gap exists, nerve grafting remains the gold-standard treatment but creates a second surgical site, sensory deficit at the donor site, possible neuroma formation and has limited availability. Current commercially available synthetic and resorbable nerve conduit alternatives are reported to be rigid and inflexible. This study will set out to examine the first-in-man use of a new nerve conduit device 'Polynerve' to repair small nerve gaps in digital sensory nerves of the hand. Polynerve is a degradable co-polymer of poly-ε-caprolactone and poly-l-lactic acid, which is shaped as a cylinder that has greater tensile strength, flexibility and less acidic degradation compared with current commercially available synthetic nerve conduits. In addition, it has a novel micro-grooved internal lumen that aids Schwann cell ingress and alignment to improve nerve regeneration. In total, 17 eligible participants will be recruited to undergo repair of a transected sensory nerve of the hand using the Polynerve device. All participants that receive the nerve conduit device will be followed for a period of 12 months post-surgery. The primary endpoint is safety of the device and the secondary endpoint is degree of sensory nerve regeneration through the conduit assessed using standard sensory testing (2-PD, WEST monofilament testing and locognosia). The 'UMANC' trial is a single-centre UK-based, prospective, unblinded, phase I clinical trial of a novel nerve conduit device. We aim to demonstrate the safety of Polynerve as a synthetic, biodegradable nerve conduit and improve the treatment options available to patients with significant nerve injuries. Clinicaltrials.gov: NCT02970864; EudraCT: 2016-001667-37.
周围神经损伤很常见，在英国每年约有9000例。主要受影响的是年轻的在职人员，这会对健康和社会产生重大影响。功能恢复通常较差，伴有手部感觉受损、运动功能减退以及疼痛和对寒冷不耐受。当存在神经间隙时，神经移植仍然是金标准治疗方法，但会产生第二个手术部位、供体部位的感觉缺陷、可能形成神经瘤且可用性有限。据报道，目前市售的合成和可吸收神经导管替代品都很僵硬且缺乏灵活性。本研究将着手研究一种新型神经导管装置“Polynerve”在人体中的首次应用，以修复手部指感觉神经的小神经间隙。Polynerve是聚ε-己内酯和聚-L-乳酸的可降解共聚物，其形状为圆柱体，与目前市售的合成神经导管相比，具有更大的拉伸强度、柔韧性和更低的酸性降解。此外，它有一个新颖的微槽内腔，有助于雪旺细胞进入和排列，以促进神经再生。总共将招募17名符合条件的参与者，使用Polynerve装置对手部横断的感觉神经进行修复。所有接受神经导管装置的参与者将在术后随访12个月。主要终点是该装置的安全性，次要终点是通过使用标准感觉测试（两点辨别觉、WEST单丝测试和位置觉）评估的通过导管的感觉神经再生程度。“UMANC”试验是一项在英国单中心进行的、前瞻性、非盲法的I期新型神经导管装置临床试验。我们的目标是证明Polynerve作为一种合成的、可生物降解的神经导管的安全性，并改善为严重神经损伤患者提供的治疗选择。Clinicaltrials.gov：NCT02970864；EudraCT：2016-001667-37。
