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

具有程序化释放神经营养因子的分层结构导管用于修复粗神经的大缺损

• 批准号: 10579569
• 负责人: NICHOLAS M BOULIS
• 金额: $ 33.94万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10579569
• 关键词: Acceleration; Affect; Anatomy; Animals; Autologous Transplantation; Axon; Benchmarking; Biochemical; Biochemistry; Biomedical Engineering; Cellular biology; Chick Embryo; Clinic; Cues; Defect; Distal; Encapsulated; Engravings; Face; Facial nerve structure; Fatty Acids; Fiber; Filopodia; Goals; Growth; Growth Cones; Half-Life; Health; Individual; Injury; Kinetics; Knowledge; Lesion; Masks; Mechanics; Modeling; Motor; Nanotechnology; Nerve; Nerve Regeneration; Neurites; Neurosurgeon; Operative Surgical Procedures; Performance; Peripheral Nerves; Peripheral nerve injury; Persons; Procedures; Process; Productivity; Protocols documentation; Quality of life; Rattus; Recovery of Function; Research; Research Personnel; Route; Scientist; Site; Spinal Ganglia; Structure; Surface; Surgical sutures; System; Technology; Testing; Thick; Translating; Tubular formation; United States; Universities; Welding; Work; biocompatible polymer; biodegradable polymer; controlled release; crosslink; design; efficacy evaluation; fabrication; fetal; healing; improved; in vitro Model; injury and repair; innovation; loss of function; man; medical schools; nanoscale; nerve repair; nerve stem cell; neurosurgery; neurotrophic factor; novel; particle; porcine model; repaired; sciatic nerve

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.

项目概要/摘要 该项目旨在开发、验证和转化一类新型神经引导导管（NGC），用于 通过恢复粗大周围神经的连续性和功能，对粗大的周围神经进行手术修复和愈合。 该研究团队包括来自纳米技术系的一位创新且富有成效的专家 佐治亚理工学院的生物医学工程和顶尖的神经外科医生和科学家 埃默里大学医学院神经外科系。以解剖结构为指导 周围神经，以及参与损伤和修复的生物化学和细胞生物学，研究人员 使用生物相容性静电纺丝纤维设计、制造和验证多管导管 (mNGC) 和可生物降解的聚合物。 mNGC 通常由 3 或 7 个蜂窝状阵列包裹而成 大型单管导管内装有小型单管导管。每个导管的壁包含三个 层：单轴排列的纤维纵向引导内层和外层的轴突延伸， 与夹在中间的随机纤维（在交叉点焊接）一起以避免撕裂或塌陷 手术期间。除了与排列的纤维相关的地形提示外，每根纤维的表面 内层进一步刻有纵向纳米凹槽，通过提供更多的能量来加速神经突的生长 生长锥中丝状伪足的传感目标和接触垫。此外，神经营养因子（NTF） 装载在天然脂肪酸的中空微粒中，然后光交联以形成单向 沿着导管的降解半衰期梯度。拟议的活动大致分为三大类 推力：i）控制由天然脂肪酸制成的中空微粒的降解速率，从而释放 通过光交联的 NTF 动力学； ii) 评估 3 合 1 mNGC 在大鼠坐骨神经修复中的作用 模型; iii) 在猪模型中评估 7 合 1 mNGC 的面神经修复效果。 NGC 是 由于排列纤维产生的协同效应，预计会增强神经再生， 纤维表面纳米沟槽，NTF稳定供应，提升健康品质 周围神经损伤患者的生命。