Fiber-Enhanced Nerve Guide

描述（由申请人提供）：Regeneration Matrix的技术获得了格鲁吉亚理工学院的许可，能够设计下一代神经导引产品，以桥接因创伤、肿瘤切除或重建手术而产生的大的周围神经间隙。基本技术包括一个“核心”的基于聚合物的薄膜，含有对齐的可生物降解的电纺聚合物纤维（直径400- 600纳米），放置在管状导管内。该10微米厚的膜仅占据神经套囊/导管的横截面积的0.3%，并且通过促进宿主施旺细胞有效迁移到差距中，显著增强了可以用导管桥接的临界间隙。此外，这种纤维增强神经导引器（FE神经导引器）能够桥接临界尺寸的神经间隙，而无需添加任何外源性蛋白质，因此能够将其归类为器械，并且基于同品种神经袖带，我们有信心将其FDA批准为器械。周围神经损伤是一个严重的临床问题。每年约有250，000 - 300，000例周围神经损伤病例报告。周围神经修复的临床金标准使用从患者供体部位采集的神经。这些自体移植物是目前最好的临床桥接选择;然而，并发症，如可用性有限和神经瘤形成降低了它们的吸引力。人工方法仅使用神经袖带（管状导管），其在技术上被批准用于桥接高达30 mm的间隙，但由于缺乏有效性，很少使用超过10 mm的间隙。使用纳米支架薄膜的FE神经导引器解决了临界尺寸外周神经间隙的这一缺点，并与神经袖带相比显著增强了再生。在用聚丙烯腈-甲基丙烯酸酯共聚物纤维建立了概念证明之后，在此我们建议在该STTR应用的I期中评价可降解纤维增强神经袖带。基于自由操作分析，我们选择使用聚己内酯（一种可降解聚合物）制造该器械。使用严格的组织学、行为学和电生理学技术，在该I期STTR应用中，我们将在啮齿动物模型中使用临界尺寸的15 mm外周神经间隙，评价PCL-PCL增强型PCL神经导管支架相对于a）临床金标准（自体移植物）和B）市售领先神经套管（胶原NeuroGen神经导向器）的性能。 公共卫生相关性：仅在美国，每年就有超过25万例外周神经损伤。这项I期研究将促进新一代神经袖带的开发，用于治疗周围神经损伤。我们有信心，我们的可生物降解的神经袖将表现明显优于现有的神经导管，并大大改善周围神经损伤后的结果。

DESCRIPTION (provided by applicant): Regeneration Matrix's technology, licensed from Georgia Tech, enables the design of a next generation nerve guide product to bridge large peripheral nerve gaps created due to trauma, tumor resection, or reconstructive surgery. The fundamental technology consists of a 'core' nanofiber based film, containing aligned biodegradable electrospun polymeric fibers (diameter 400-600nm), placed inside a tubular conduit. This 10 micron thick film occupies only 0.3% of the cross-sectional area of the nerve cuff/conduit and yet by facilitating efficient migration of host Schwann cells into the gap, significantly enhances the critical gap that can be bridged with conduits. Additionally, this fiber enhanced nerve guide (FE Nerve Guide) is able to bridge critically sized nerve gaps without the addition of any exogenous proteins, enabling its classification as a device and based on the predicate nerve cuffs, we are confident of their FDA approval as a device. Peripheral nerve injuries present a serious clinical problem. Around 250,000-300,000 peripheral nerve trauma cases are reported every year. The clinical gold standard for peripheral nerve repair uses nerves harvested from patient donor sites. These autografts are the best clinical bridging option available today; however, complications such as limited availability and neuroma formation reduce their appeal. Manufactured approaches use nerve cuffs (tubular conduits) alone which are technically approved for bridging gaps up to 30mm, but they are seldom used beyond 10mm gaps because of lack of efficacy. The FE Nerve Guide using nanoscaffold film(s) addresses this shortcoming in critically sized peripheral nerve gaps, and significantly enhances regeneration when compared to nerve cuffs. Having established the proof of concept with a polyacrylonitrile-methacrylate co-polymeric fibers, here we propose to evaluate a degradable fiber enhanced nerve cuff in phase I of this STTR application. Based on a freedom to operate analysis, we have have chosen to fabricate this device with polycaprolactone, a degradable polymer. Using rigorous histological, behavioral and electrophysiological techniques, in this phase I STTR application, we will evaluate the performance of a PCL-nanofiber enhanced PCL nerve conduit scaffold against a) the clinical gold standard, the autograft; and b) the leading nerve cuff in the market, the collagen NeuroGen nerve guide, using a critically sized 15mm peripheral nerve gap in a rodent model. PUBLIC HEALTH RELEVANCE: Over 250,000 peripheral nerve injuries occur every year in the US alone. This phase I study will facilitate the development of a new generation of nerve cuffs for the treatment of peripheral nerve injuries. We are confident that our biodegradable nerve cuff will perform significantly better than existing nerve conduits and substantially improve outcomes after peripheral nerve injury.