Rapid 3D-printing of Multi-functional Adaptive Nerve Conduits

多功能自适应神经导管的快速3D打印 PI建议开发一种用于制造三维（3D）神经导管的创新平台 具有生物因子（生长因子、神经元干细胞和 细胞外基质（ECM））。这种快速3D打印平台采用动态掩模， 无需扫描即可同时对整个层进行光聚合并创建3D管道 打印速度提高1,000倍，打印分辨率提高100倍 与传统的基于打印机的3D打印机相比。透明质酸（HA），ECM成分，将被 修改为3D打印。HA是一种长链糖样分子，显示与伤口愈合相容 和神经再生。因为它是自然发生在体内，并具有微不足道的物种间 在另一变型中，HA是用于神经导管的极好的候选生物材料。神经干细胞与生长 将在导管中打印因子以帮助神经修复。 在R21阶段，PI将开发快速3D打印系统，合成HA材料， 表征3D打印的HA导管。然后，研究小组将这些神经导管植入小鼠体内， 显示神经纤维沿着导管的孔从近端到远端的生长 证明由于细胞的生长和再生， 神经纤维在R21阶段成功完成这些任务和里程碑后， 在R33阶段，将进一步开发快速3D打印过程，以创建“设计师”神经导管， 物理、化学和生物特性的精确时空控制以及使用这种设计器 用于体内动物研究的导管。这里开发的概念和技术将使我们能够创建 精确的，预先设计的生长因子和神经元干细胞的分布， 使我们能够研究它们对具有复杂结构的管道内的神经细胞引导的影响。 该项目将由一个团队的合作人才，包括陈博士谁是领先的 3D打印的专家和生物打印的先驱，以及Nguyen博士，他是一位在两个领域都获得董事会认证的领导者。 和颈部外科和神经耳科/颅底外科，是加州大学面神经诊所主任 圣地亚哥阮博士有一个专门从事面神经麻痹的临床实践， 专业知识和基础科学研究经验。

Rapid 3D-printing of Multi-functional Adaptive Nerve Conduits The PIs propose to develop an innovative platform for the fabrication of 3-dimensional (3D) nerve conduits with precise spatial and temporal distribution of biological factors (growth factors, neuron stem cells and extracellular matrix (ECM)). This rapid 3D printing platform employs a dynamic mask for photopolymerization of an entire layer simultaneously without scanning and create 3D conduits continuously, resulting in 1,000 times faster in printing speed and 100 times better in printing resolution compared to traditional nozzle-based 3D printers. Hyaluronic acid (HA), an ECM component, will be modified for 3D printing. HA is a long-chain sugar-like molecule shown to be compatible with wound healing and nerve regeneration. Because it is naturally occurring in the body and has negligible inter-species variation, HA is an excellent candidate biomaterial to use for nerve conduits. Neuron stem cells and growth factors will be printed in the conduits to aid nerve repair. In the R21 phase, the PIs will develop the rapid 3D printing system, synthesize the HA materials and characterize the 3D printed HA conduits. The team will then implement these nerve conduits into mice to demonstrate growth of the nerve fibers along the bore of the conduit from proximal to distal end and also demonstrate reduction in time to functional recovery due to conduit-assisted growth and regeneration of the nerve fiber. Upon successful completion of these tasks and milestones in the R21 phase, subsequent work in the R33 phase will further develop the rapid 3D printing process to create "designer" nerve conduits with precise spatio-temporal control of physical, chemical, and biological properties and use such designer conduits for in vivo animal studies. The concepts and techniques developed herein would allow us to create precise, pre-designed distributions of growth factors and neuron stem cells with microscale resolution and enable us to investigate their effects on nerve cell guidance inside a conduit with complex architectures. The project will be carried out by a team of collaborative talents, including Dr. Chen who is a leading expert in 3D printing and a pioneer in bioprinting, and Dr. Nguyen who is a is board certified in both Head and Neck Surgery and Neurotology/Skull Base Surgery and is the Director of the Facial Nerve Clinic at UC San Diego. Dr. Nguyen has a clinical practice specializing in facial nerve paralysis and brings both clinical expertise as well as basic science research experience to this project.