3D Bioprinted Spinal Cord Organoids as a Relay System for Spinal Cord Injury

项目总结/摘要 这项研究的长期目标是确定成功细胞的作用机制 移植治疗慢性脊髓损伤（SCI），并将这些知识从 把长凳搬到病人床边。人类SCI目前没有有效的治疗方法，任何新的 治疗将对公众健康产生重大影响。本报告的总体目标 建议是确定是否移植区域特异性生物打印的脊髓神经 祖细胞（sNPC）与3D打印支架的组合可以导致 损伤的成年大鼠脊髓内的功能性神经元网络。我们有三个具体的 目标。第一个目标是优化生物材料和3D打印支架的设计 作为生物打印中使用的载有细胞的生物墨水。第二个目标是确定最佳单元格 在支架内两种类型的区域特异性sNPC的构型，以形成功能性的 神经网络第三个目的是在横断损伤的大鼠模型中测试我们的支架， 确定我们的细胞是否可以在损伤部位提供中继系统， 这将导致功能恢复。我们将进行详细的功能，组织学， 电生理分析，以阐明我们的组合治疗的机制。的 科学的前提是，在提供基质（细胞）用于治疗中存在协同关系。 中继系统在整个受伤部位，并优化这与导管（脚手架），提供一个 神经元信号传导的有效中继导致功能恢复。

PROJECT SUMMARY/ABSTRACT The long-term goal of this research is to define the mechanisms of action of a successful cell transplantation therapy for chronic spinal cord injury (SCI) and to translate this knowledge from bench to bedside for patients. Human SCI currently has no effective treatment, and any new treatments would have a significant impact on public health. The overall objective of this proposal is to determine whether transplantation of regionally specific bioprinted spinal neural progenitor cells (sNPCs) in combination with a 3D printed scaffold can result in the formation of functional neuronal networks within the injured adult rat spinal cord. We have three specific aims. The first aim is to optimize the biomaterial and design of the 3D printed scaffold, as well as the cell-laden bioink utilized in bioprinting. The second aim is to determine the optimal cell configuration of two types of regionally specific sNPCs within the scaffold to form functional neuronal networks. The third aim is to test our scaffold in a rat model of transection injury to determine whether our cells can provide a relay system across the site of injury, and whether this will result in functional recovery. We will perform detailed functional, histological, and electrophysiological analyses to elucidate the mechanisms of our combinatorial treatment. The scientific premise is that there is a synergistic relationship in providing the substrate (cells) for a relay system across the injury site and optimizing this with a conduit (scaffold), providing an effective relay for neuronal signaling leading to functional recovery.