3D Printed Scaffolds for Primate Spinal Cord Injury Repair

用于灵长类脊髓损伤修复的 3D 打印支架

• 批准号: 10331799
• 负责人: Yacov Koffler
• 金额: $ 63.43万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10331799
• 关键词: 3-Dimensional; 3D Print; Acute; American; Anatomy; Animals; Architecture; Axon; Biomimetics; Cervical; Cervical spinal cord injury; Cervical spinal cord structure; Clinical Trials; Contusions; Corticospinal Tracts; Data; Disease; Electrophysiology (science); Esthesia; Exercise; Feasibility Studies; Forelimb; Grant; Hand functions; Hindlimb; Home; Hour; Human; Implant; Individual; Injury; Lead; Lesion; Macaca mulatta; Magnetic Resonance Imaging; Medical; Modeling; Monkeys; Motor; Natural regeneration; Nervous System Trauma; Neurophysiology - biologic function; Neurosciences; Outcome; Performance; Perfusion; Primates; Printing; Recovery; Recovery of Function; Reporting; Robotics; Rodent; Science; Shapes; Site; Spinal; Spinal Cord; Spinal Cord Contusions; Spinal Cord transection injury; Spinal cord damage; Spinal cord injury; Spinal cord injury patients; Surgical Decompression; Suspensions; System; Technology; Time; Tissues; Vascularization; Vision; Work; axon growth; axon regeneration; base; biocompatible scaffold; biomaterial compatibility; clinically relevant; disability; effective therapy; efficacy evaluation; efficacy study; functional outcomes; hand rehabilitation; implantation; improved; injury and repair; innovation; nerve stem cell; nonhuman primate; relating to nervous system; safety study; scaffold; scale up; severe injury; spinal cord regeneration; stem cell biology; stem cell survival; stem cell technology; stem cell therapy; stem cells; synaptogenesis

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.

项目概要/摘要 近 30 万美国人遭受过某种形式的脊髓损伤 (SCI)，有效的治疗 缺乏促进神经功能恢复的疗法。我们的总体愿景是创建一个 离体组织可以替代受损的脊髓并能够形成新的中继电路 跨越甚至严重受伤的部位。我们使用 3D 打印仿生支架进行广泛的啮齿动物研究 表明这种方法可以在完成后导致电生理和功能恢复 脊髓横断，最严重的脊髓损伤模型。 该项目旨在评估装载人体的 3D 打印仿生支架的功效 神经祖细胞并急性植入长期临床相关的非人类灵长类动物体内 颈脊髓挫伤模型。 该项目有 2 个目标： 1. 解剖结果分析 - 生物相容性、整合、降解、 血管化、宿主轴突再生成支架以及神经祖细胞衍生 轴突从支架生长到宿主中。 2. 功能结果分析。动物将根据右任务进行功能评估 手部功能，包括布林克曼板、家用笼式机器人操作、前肢 和后肢在开放场地/练习场中的使用以及感觉。 资助的成功绩效结果可能会导致临床试验，从而产生巨大的影响。