Fiber-Enhanced Nerve Guide

纤维增强神经导管

• 批准号: 8001188
• 负责人: Ravi V. Bellamkonda
• 金额: $ 19.93万
• 依托单位: REGENERATION MATRIX, LLC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8001188
• 关键词: Address; Adult; Area; Autologous Transplantation; Behavioral; Biocompatible Materials; Brain-Derived Neurotrophic Factor; Caliber; Case Study; Classification; Clinical; Collagen; Data; Defect; Development; Devices; Engineering; Excision; Extracellular Matrix Proteins; Fiber; Film; Freedom; Generations; Gold; Growth Factor; Harvest; Implant; Knowledge; Laboratories; Laminin; Length; Licensing; Malignant Neoplasms; Marketing; Measures; Methacrylates; Modeling; Morbidity - disease rate; Natural regeneration; Nerve; Neuroma; Outcome; Patients; Performance; Peripheral Nerves; Peripheral nerve injury; Pharmaceutical Preparations; Phase; Polymers; Proteins; Rattus; Reconstructive Surgical Procedures; Relative (related person); Research; Rodent Model; Schwann Cells; Site; Small Business Technology Transfer Research; Surgeon; Techniques; Technology; Testing; Thick; Trauma; Tube; Tubular formation; base; behavior measurement; biodegradable polymer; biomaterial compatibility; commercialization; design; improved; migration; nanofiber; nanofilament; nerve gap; next generation; phase 1 study; polyacrylonitrile; polycaprolactone; public health relevance; repaired; scaffold; scale up; submicron; tumor

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.

描述（由申请人提供）：佐治亚理工学院获得许可的调查矩阵的技术，使下一代神经指南产品的设计可以桥接由于创伤，肿瘤切除或重建手术而产生的较大的外围神经间隙。基本技术由基于“核心”纳米纤维的膜组成，其中包含位于管状导管内的可相反的可生物降解的电纺多聚合物纤维（直径为400-600nm）。这10微米厚的薄膜仅占神经袖口/导管的横截面面积的0.3％，但通过促进宿主雪旺氏细胞的有效迁移到间隙中，可以显着增强可以与导管弥合的临界差距。此外，该纤维增强的神经指南（FE神经指南）能够在不添加任何外源蛋白质的情况下桥接较大的神经间隙，从而使其作为设备的分类并基于谓词神经袖口，我们对他们的FDA批准充满信心。周围神经损伤带来了严重的临床问题。每年报告约25万-300,000外周神经创伤病例。周围神经修复的临床金标准使用从患者供体部位收获的神经。这些自体移植是当今可用的最佳临床桥接选项。但是，诸如有限的可用性和神经瘤形成之类的并发症降低了其吸引力。制成的方法仅使用神经袖口（管状导管），这些神经袖口在技术上被批准用于弥合30mm的间隙，但由于缺乏功效，它们很少被超过10mm的间隙使用。使用Nanoscaffold膜的FE神经指南解决了在批判尺寸的外周神经间隙中的这种缺陷，与神经袖口相比，这种缺点显着增强了再生。通过聚丙烯丙烯酸 - 丙烯酸酯共丙烯酸酯共晶纤维建立了概念证明，我们在这里建议在此STTR应用的I期中评估可降解的纤维增强神经袖口。基于操作分析的自由，我们选择用可降解聚合物的多碳酸酯来制造该设备。使用严格的组织学，行为和电生理技术，在此I阶段ISTTR应用中，我们将评估PCL-纳米纤维增强的PCL神经导管支架的性能针对A）临床金标准，即自体移植； b）市场上胶原蛋白神经神经指南的主要神经袖带，使用啮齿动物模型中的15mm外周神经间隙。 公共卫生相关性：仅在美国，每年都会发生超过25万个周围神经损伤。这一I阶段的研究将促进新一代神经袖口的发展，以治疗周围神经损伤。我们相信，我们的可生物降解神经袖带的表现将比现有的神经导管高得多，并且在周围神经损伤后大大改善了预后。