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

多功能自适应神经导管的快速三维打印 PIS建议开发一种用于制造三维(3D)神经导管的创新平台 具有精确的生物因素(生长因子、神经干细胞和 细胞外基质(ECM))。这款快速3D打印平台采用动态蒙版 无需扫描即可同时实现整个层的光聚合，并创建3D管道 连续打印，打印速度提高1000倍，打印分辨率提高100倍 相比传统的基于喷嘴的3D打印机。ECM的组成部分透明质酸(HA)将被 针对3D打印进行了修改。HA是一种长链糖状分子，被证明与伤口愈合相容 和神经再生。因为它是自然存在于体内的，其物种间的差异可以忽略不计。 因此，HA是一种很好的神经导管候选生物材料。神经干细胞与生长 这些因子将被印在导管中，以帮助神经修复。 在R21阶段，PIS将开发快速3D打印系统，合成HA材料和 对3D打印的HA导管进行表征。然后，研究小组将把这些神经导管植入小鼠体内 显示神经纤维沿导管内径从近端到远端的生长，还 证明由于导管辅助的生长和再生减少了功能恢复的时间 神经纤维。在成功完成R21阶段的这些任务和里程碑后，后续工作 在R33阶段，将进一步开发快速3D打印工艺，以创建具有 物理、化学和生物特性的精确时空控制以及使用这样的设计器 活体动物研究的管道。这里开发的概念和技术将允许我们创建 精确、预先设计的生长因子和神经干细胞分布，具有微尺度分辨率和 使我们能够研究它们在具有复杂架构的管道内对神经细胞指导的影响。 该项目将由一个合作人才团队实施，其中包括领先的 3D打印专家和生物打印的先驱，Nguyen博士是一名获得双头认证的IS董事会成员 和颈部外科和神经病学/颅底外科，是加州大学面神经诊所的主任 圣地亚哥。阮医生有专门治疗面神经麻痹的临床经验，并将这两种临床经验 为这个项目提供专业知识以及基础科学研究经验。

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.