3D Printed Scaffolds for Primate Spinal Cord Injury Repair

项目摘要/摘要 近30万美国人遭受了某种形式的脊髓损伤(SCI)， 目前尚缺乏促进神经功能恢复的治疗方法。我们的总体愿景是创建一个 可替代受损脊髓并能形成新的继电回路的体外组织 甚至是严重受伤的地点。我们广泛的啮齿动物使用3D打印的仿生支架 结果表明，此入路可在完全性手术后恢复电生理和功能。 脊髓横断术是脊髓损伤最严重的模型。 该项目旨在评估3D打印仿生支架的效果，负载人类 神经前体细胞，并急性移植到长期临床相关的非人类灵长类动物中 颈髓挫伤模型的建立。 这个项目有两个目标： 1.解剖结果分析--生物相容性、整合性、降解性、 血管化、宿主轴突再生进入支架和神经前体细胞来源 轴突从支架长入宿主。 2.功能结局分析。将对动物进行功能评估，执行正确的任务- 手功能，包括Brinkman板，家庭笼式机器人操作，前肢 以及后肢在开阔场地/练习场中的使用，以及感觉。 赠款的成功执行结果可能会导致临床试验，从而产生很大的影响。

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.