3D Printed Scaffolds for Primate Spinal Cord Injury Repair

项目概要/摘要 近30万美国人患有某种形式的脊髓损伤（SCI）， 缺乏促进神经功能恢复的疗法。我们的总体愿景是创造一个 可以替代受损脊髓并能够形成新的中继电路的离体组织 甚至是严重受伤的部位。我们对3D打印仿生支架的广泛啮齿动物研究 表明这种方法可以在完全恢复后导致电生理和功能恢复。 脊髓横断是最严重的脊髓损伤模型。 该项目旨在评估3D打印仿生支架的功效， 神经祖细胞，并在长期临床相关的非人灵长类动物中急性植入 颈脊髓挫伤模型。 该项目有两个目标： 1.解剖结局分析-生物相容性、整合、降解， 血管化，宿主轴突再生到支架中，以及神经祖细胞衍生的 轴突从支架长出进入宿主。 2.功能结果分析。将对动物进行功能评估，以完成正确的任务- 手部功能，包括Brinkman板、基于家庭笼的机器人操作、前肢 和后肢在开阔场地/练习场地中的使用，以及感觉。 赠款的成功绩效结果可能导致临床试验，产生很大的影响。

Project Summary/Abstract Nearly 300,000 Americans have sustained some form of spinal cord injury (SCI), and effective therapies to promote recovery of neural function are lacking. Our overarching vision is to create an ex-vivo tissue that can replace the damaged spinal cord and enable formation of new relay circuits across sites of even severe injury. Our extensive rodent work with 3D printed biomimetic scaffolds shows that this approach can result in electrophysiological and functional recovery after complete spinal cord transection, the most severe model of spinal cord injury. This project aims to assess the efficacy of 3D printed biomimetic scaffolds, loaded with human neural progenitor cells and implanted acutely, in a long-term clinically relevant, non-human primate model of cervical spinal cord contusion. There are 2 objectives to this project: 1. Analysis of anatomical outcomes - Biocompatibility, integration, degradation, vascularization, host axon regeneration into the scaffold, and neural progenitor cell-derived axon outgrowth from the scaffold into the host. 2. Analysis of functional outcomes. Animals will be functionally assessed on tasks of right- hand function, including Brinkman board, home cage-based robotic manipulation, forelimb and hindlimb use in an open field/exercise enclosure, and sensation. Successful performance outcomes of the grant may lead to clinical trials, with resulting high impact.