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.

项目摘要/摘要 该项目旨在开发，验证和翻译一类新的神经引导导管（NGC）， 通过恢复周围神经的连续性和功能来修复和愈合周围神经的大缺损。 该研究小组包括一个创新和生产力的纳米技术专家从该部 格鲁吉亚理工学院的生物医学工程博士和来自美国的顶级神经外科医生和科学家， 埃默里大学医学院神经外科系。在解剖结构的指导下， 周围神经，以及参与损伤和修复的生物化学和细胞生物学， 设计，制造和验证多管状导管（mNGC）使用从生物相容性 和可生物降解的聚合物。mNGC通常通过包裹3或7个纳米颗粒的蜂窝状阵列来构建。 在大的单管导管内的小的单管导管。每个管道的壁包含三个 层：单轴排列的纤维以纵向引导内层和外层的轴突延伸， 以及夹在其间的随机纤维（在交叉点处焊接）以避免撕裂或塌陷 在手术中。除了与排列的纤维相关的地形线索外，在纤维中的每个纤维的表面也是如此。 内层进一步刻有纵向纳米凹槽，以通过提供更多的 传感目标和接触垫连接到生长锥中的丝状伪足。此外，神经营养因子（NTFs） 被装载在天然脂肪酸的中空微粒中，然后光交联以产生单向 降解半衰期的梯度沿着导管。拟议的活动大致分为三大类 i）控制由天然脂肪酸制成的中空微粒的降解速率， ii）评估三合一mNGC用于大鼠坐骨神经修复的动力学 iii）评估7合1 mNGC在猪模型中的面神经修复。NGC是 预期由于排列的纤维产生的协同效应而增强神经再生， 纤维表面的纳米凹槽，以及NTFs的稳定供应，提高了健康和质量 对于受周围神经损伤折磨的人来说，