Hierarchically-Structured Conduits with Programmed Release of Neurotrophic Factors for Repairing Large Defects in Thick Nerves

项目摘要/摘要 该项目旨在开发、验证和翻译一种新型的神经引导导管(NGCs)，用于 通过恢复粗大周围神经的连续性和功能来修复和愈合粗大周围神经的外科手术。 研究小组包括一位创新和多产的纳米技术专家，来自美国能源部 佐治亚理工学院的生物医学工程和来自 埃默里大学医学院神经外科。在解剖结构的指导下 外周神经，以及与损伤和修复有关的生物化学和细胞生物学，研究人员 设计、制造和验证多管导管(MNGCs)，使用从生物兼容材料中电纺的纤维 和可生物降解的聚合物。MNGC通常通过包裹3个或7个蜂窝阵列来构建 大型单管导管内的小型单管导管。每条管道的壁上都有三个 层：单轴排列的纤维，以纵向引导内层和外层的轴突延伸， 以及夹在中间的随机纤维(焊接在交叉点)，以避免撕裂或坍塌 在手术期间。除了与排列的纤维相关联的地形线索外， 内层进一步刻有纵向纳米凹槽，通过提供更多 感测目标和接触垫至生长锥体中的丝状基座。此外，神经营养因子(NTF) 都装载在中空的天然脂肪酸微粒中，然后光交联成单向的 沿管道的降解半衰期的梯度。拟议的活动大致分为三大类 推动：i)控制天然脂肪酸制成的中空微粒的降解率，从而释放 光交联法测定神经营养因子的动力学；ii)评价3-in-1mNGCs对大鼠坐骨神经修复的作用 以及iii)在猪模型中评估7合1 mNGCs用于面神经修复。非政府组织是 由于排列的纤维产生的协同效应，预计将增强神经再生， 纤维表面的纳米槽，以及NTF的稳定供应，改善了健康和质量 对于受到周围神经损伤困扰的个人来说，这是一种生活方式。

PROJECT SUMMARY/ABSTRACT This project aims to develop, validate, and translate a novel class of nerve guidance conduits (NGCs) for the surgical repair and healing of large defects in thick peripheral nerves by restoring their continuity and functions. The research team includes an innovative and productive expert in nanotechnology from the Department of Biomedical Engineering at the Georgia Institute of Technology and a top neurosurgeon and scientist from the Department of Neurosurgery at Emory University School of Medicine. Guided by the anatomic structure of peripheral nerve, as well as the biochemistry and cell biology involved in injury and repair, the investigators design, fabricate, and validate multi-tubular conduits (mNGCs) using fibers electrospun from a biocompatible and biodegradable polymer. The mNGC is typically constructed by wrapping a honeycomb array of 3 or 7 small, single-tubular conduits inside a large, single-tubular conduit. The wall of each conduit contains three layers: uniaxially-aligned fibers to longitudinally guide axonal extension for both the inner and outer layers, together with random fibers (welded at cross points) sandwiched in between to circumvent tearing or collapsing during surgery. Besides the topographic cue associated with the aligned fibers, the surface of each fiber in the inner layer is further engraved with longitudinal nanogrooves to accelerate neurite outgrowth by providing more sensing targets and contact pads to the filopodia in the growth cone. In addition, neurotrophic factors (NTFs) are loaded in hollow microparticles of natural fatty acids and then photo-cross-linked to create a unidirectional gradient in degradation half-life along the conduit. The proposed activities are broadly divided into three major thrusts: i) controlling the degradation rate of hollow microparticles made of natural fatty acids and thus release kinetics of NTFs through photo-cross-linking; ii) evaluating the 3-in-1 mNGCs for sciatic nerve repair in a rat model; and iii) assessing the 7-in-1 mNGCs for facial nerve repair in a porcine model. The NGCs are anticipated to augment nerve regeneration as a result of the synergistic effect arising from the aligned fibers, the nanogrooves on the surface of the fibers, and the steady supply of NTFs, improving the health and quality of life for individuals afflicted by peripheral nerve injuries.