Fibrous Templates for Directed Nerve Regeneration

用于定向神经再生的纤维模板

• 批准号: 7474015
• 负责人: JOSEPH M. COREY
• 金额: $ 17.93万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7474015
• 关键词: Acids; Adhesions; Afferent Neurons; Autologous Transplantation; Axon; Binding; Caliber; Cell-Matrix Junction; Cells; Characteristics; Coculture Techniques; Distal; Extracellular Matrix Proteins; Fiber; Growth; Growth Factor; Inferior; Knowledge; Length; Mechanics; Methods; Modeling; Morbidity - disease rate; Motor; Motor Neurons; Natural regeneration; Nerve; Nerve Regeneration; Neurites; Neurons; Numbers; Operative Surgical Procedures; Peripheral Nerves; Play; Polyglycolic Acid; Polylysine; Polymers; Process; Production; Protein Binding Domain; Proteins; Purpose; Rattus; Research Personnel; Role; Schwann Cells; Solvents; Somatomedins; Spinal Cord; Spinal Ganglia; Structure; Supporting Cell; System; Testing; axon regeneration; biodegradable polymer; nano; nerve autograft; neuronal cell body; neuronal survival; polylactic acid-polyglycolic acid copolymer; programs; repaired; research study; scaffold; size; success; tool

DESCRIPTION (provided by applicant): Surgical repair of peripheral nerve transection is dependent on nerve autografts that produce morbidity and are often insufficient in number or size. A substitute for grafting is the nerve guide, developed to direct regenerating axons and support cells from proximal to distal ends of a transected nerve. Most nerve guides produce inferior results, even when filled or coated with extracellular matrix proteins (ECM) or growth factors that promote neurite outgrowth. The best of these have approached the success of autografts by slowly releasing growth factors and ECM from a resorbable polymer. Although topographical features play a large role in guiding neurites, only a handful of investigators have used polymer fibers to direct regenerating axons. Methods for producing aligned fibers with nano- and micro-scale diameters in which growth factors and ECM can be incorporated, have been developed for the purpose of neural regeneration. A proposal to fabricate and test these fibers is presented. Specific aim 1 begins with production and characterization of aligned fibers from degradable polymers. Fibers will be fabricated with varying alignments, diameters and inter-fiber spacing. Growth factors and ECM binding domains will be immobilized in the fibers. Mechanical strength, crystalline structure, spacing, alignment, and size of fibers will be characterized. A method to place fibers into a nerve guide will be developed. In specific aim 2, these fibers will be tested for their ability to promote adhesion of and neurite outgrowth from dissociated motor neurons and dorsal root ganglia (DRG) neurons in primary culture. Neuron cell body attachment, and neurite length and alignment will be quantified as functions of fiber material, alignment, diameter, spacing, and incorporated growth factor and ECM. The effect of Schwann cells on neurite outgrowth will be examined in co-culture experiments. Specific aim 3 continues this testing using explant models. Both sensory neurons from DRG explants and motor neurons from spinal cord explants will be used. Effects of Schwann cells on neurite outgrowth will be examined in this aim, also. It is hoped that this project will further knowledge of both the production of advanced fibrous scaffoldings and their potential to be harnessed as a tool for nerve regeneration.

描述（由申请人提供）： 外围神经横向的手术修复取决于产生发病率且数量或大小不足的神经自体移植。嫁接的替代品是神经指南，开发用于将轴突和支撑细胞从跨性别神经的近端到远端。即使在填充或涂有细胞外基质蛋白（ECM）或促进神经突生长的生长因子时，大多数神经指南也会产生较低的结果。其中最好的方法通过从可吸收性聚合物中缓慢释放生长因子和ECM来接近自体移植的成功。尽管地形特征在指导神经突中起着重要作用，但只有少数研究人员使用聚合物纤维来指导再生轴突。生长和微尺度直径的对齐纤维的方法，其中可以纳入生长因子和ECM，并为神经再生而开发。 提出了制造和测试这些纤维的建议。特定的目标1始于可降解聚合物的对齐纤维的生产和表征。纤维将用不同的对齐，直径和纤维间间距制成。生长因子和ECM结合域将被固定在纤维中。机械强度，晶体结构，间距，对齐和纤维大小将被表征。将开发将纤维放入神经指南中的方法。在特定的目标2中，这些纤维将测试它们在原发性培养中促进分离的运动神经元和背根神经元（DRG）神经元的粘附和神经突生长的能力。神经元细胞体的附着，神经突长度和比对将被定量为纤维材料，对齐，直径，间距以及掺入生长因子和ECM的功能。在共培养实验中将检查雪旺细胞对神经突生长的影响。特定目标3继续使用Explant模型进行此测试。将使用来自DRG外植体的感觉神经元和脊髓外植体的运动神经元。还将在此目标中检查雪旺细胞对神经突生长的影响。 希望该项目能够进一步了解先进的纤维脚手架的产生，及其作为神经再生工具的潜力。