SCI Consortium Study: 3D Printed Scaffolds for Primate Spinal Cord Injury Repair

SCI 联盟研究：3D 打印支架用于灵长类脊髓损伤修复

• 批准号: 10379167
• 负责人: Yacov Koffler
• 金额: --
• 依托单位: VA SAN DIEGO HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10379167
• 关键词: 3-Dimensional; 3D Print; Acute; Admission activity; Anatomy; Animals; Architecture; Award; Axon; Biomimetics; Caring; Cervical; Cervical spinal cord structure; Clinical; Clinical Trials; Contusions; Corticospinal Tracts; Data; Development; Disease; Electrophysiology (science); Esthesia; Exercise; Feasibility Studies; Forelimb; Future; Hand functions; Hindlimb; Home; Hospital Records; Hospitalization; Human; Implant; Individual; Injury; Lesion; Macaca mulatta; Magnetic Resonance Imaging; Mission; Modeling; Monkeys; Motor; Natural regeneration; Nervous System Trauma; Neurophysiology - biologic function; Neurosciences; Outcome; Patient Care; Perfusion; Primates; Printing; Recovery; Recovery of Function; Reporting; Robotics; Rodent; Science; Shapes; Site; Spinal Cord; Spinal Cord Contusions; Spinal Cord transection injury; Spinal cord damage; Spinal cord injury; Spinal cord injury patients; System; Technology; Time; Tissues; Treatment Cost; Vascularization; Veterans; Vision; Work; axon growth; axon regeneration; base; biocompatible scaffold; biomaterial compatibility; clinically relevant; effective therapy; efficacy evaluation; efficacy study; efficacy testing; functional outcomes; hand rehabilitation; improved; injury and repair; innovation; nerve stem cell; nonhuman primate; relating to nervous system; safety study; scaffold; scale up; severe injury; stem cell biology; stem cell survival; stem cell technology; stem cell therapy; stem cells; synaptogenesis

Project Summary/Abstract The VA provides care for approximately 26% of individuals with SCI in the U.S. Treatment costs are 6.5 times higher than the cost of treatment of an average Veteran, 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 sub-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 completion of the award will provide key data to support future clinical trials, with resulting high impact.

项目概要/摘要 VA 为美国大约 26% 的 SCI 患者提供护理。治疗费用为 6.5 比普通退伍军人的治疗费用高出数倍，以及促进康复的有效疗法 神经功能缺乏。我们的总体愿景是创造一种可以替代的离体组织 受损的脊髓，甚至能够在严重损伤的部位形成新的中继电路。我们的 使用 3D 打印仿生支架进行的广泛啮齿动物研究表明，这种方法可以带来 完全脊髓横断后的电生理和功能恢复，最严重的模型 脊髓损伤。 该项目旨在评估装载有人类神经元的 3D 打印仿生支架的功效 祖细胞并亚急性植入长期临床相关的非人类灵长类动物模型中 颈脊髓挫伤。 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、 宿主轴突再生到支架中，神经祖细胞衍生的轴突从支架中生长出来 支架进入宿主。 2. 功能结果分析。动物将根据右手任务进行功能评估 功能，包括布林克曼板、家用笼式机器人操纵、前肢和后肢 在开放场地/练习场中使用，以及感觉。 该奖项的成功完成将为支持未来的临床试验提供关键数据，从而产生高 影响。