Pre-clinical validation of 3D-printed nerve conduits for pediatric peripheral nerve repair

3D 打印神经导管用于儿科周围神经修复的临床前验证

• 批准号: 10672031
• 负责人: SHAOCHEN CHEN
• 金额: $ 63.24万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-27 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10672031
• 关键词: 18 year old; 3-Dimensional; 3D Print; Autoimmune Diseases; Autologous; Autologous Transplantation; Biocompatible Materials; Biomimetics; Birth; Body part; Brachial plexus structure; Child; Childhood; Clinical; Collection; Commercial grade; Computer-Aided Design; Data; Defect; Devices; Diabetes Mellitus; Diagnostic; Dimensions; Distal; Electrophysiology (science); Engineering; Evaluation; FDA approved; Gelatin; Generations; Geometry; Goals; Growth; Harvest; Head and neck structure; Human; Image; Implant; In Situ; Infant; Injury; Intelligence; Length; Lower Extremity; MRI Scans; Magnetic Resonance Imaging; Medical; Methods; Modeling; Monitor; Morbidity - disease rate; Mus; Nerve; Nerve Fibers; Nerve Regeneration; Nerve Tissue; Neuroma; Numbness; Operative Surgical Procedures; Paralysed; Patients; Performance; Peripheral nerve injury; Polymers; Population; Predisposition; Printing; Procedures; Process; Prognosis; Property; Recovery; Recovery of Function; Reporting; Reproducibility; Research; Shapes; Side; Site; Source; Specific qualifier value; Spinal cord injury; Structure; System; Techniques; Testing; Therapeutic; Time; Translations; Trauma; Upper Extremity; Validation; Vascularization; Work; axon growth; axon regeneration; biomaterial compatibility; bioprinting; clinical translation; commercialization; design; digital; fabrication; flexibility; head/neck injury; hydrogel scaffold; image guided; implanted sensor; injured; innovation; loss of function; manufacture; meetings; meter; nerve damage; nerve injury; nerve repair; neural; neural graft; nonhuman primate; pediatric patients; peripheral nerve repair; poly(ethylene glycol)diacrylate; pre-clinical; real time monitoring; regenerative; regenerative therapy; repaired; scaffold; sciatic nerve; sciatic nerve injury; sensor; sex; success; tumor; wireless; wireless sensor

Project Summary Peripheral nerve injuries, as a result of trauma, tumors, or other medical conditions, require 50,000-200,000 surgeries annually, and may cause complete or partial paralysis. The autograft is the current "gold standard" but requires additional procedures to harvest the graft, can be challenging to perform in a pediatric population, and often leads to neuroma formation and loss of function at the donor site. The goal of this project is to validate the materials and methods to fabricate pre-clinical polymeric three-dimensional (3D) nerve conduits with an embedded wireless sensor for continuous monitoring of functional recovery to be used in infants/children. The 3D printed vascularizable nerve conduits mimic the micro-architecture of nerve tissues, are embedded with wireless sensors for in situ monitoring, and can perform biomimetic functions to augment nerve regeneration therapies. Currently, there is no clinical solution for monitoring the success of a neural graft therapy after surgery. Specific Aim 1 will focus on optimizing 3D-bioprinted nerve conduit fabrication and performance using commercial-grade biomaterials for clinical translation. To fabricate such a conduit in this aim, we will use a Rapid Projection, Image-guided, Direct-printing (RaPID) platform that can 3D-print the entire nerve conduit in mere seconds and will match the patient’s specific size and shape. The conduit will have linear micro-channels along the length for axon growth and side micro-holes for vascularization. Specific Aim 2 will validate generation of pediatric patient-specific conduits based on volumetric defect. In this aim, we will coordinate the collection of MRI data among pediatric patients from birth to 18 years of age, both sexes, and with peripheral nerve injuries involving the head and neck, upper limbs, and lower limbs. Based upon the MRI data collected, personalized pediatric nerve conduits will be 3D bioprinted to validate the RaPID system and provide evidence for planned FDA regulatory review. Specific Aim 3 will develop a wirelessly powered and controlled sensor to detect electrical impulses across a nerve defect. In this aim, we will attach wireless sensors via a polymeric cuff design to the distal end of an injured mouse sciatic nerve to assess the rate and robustness of nerve fiber growth across the therapeutic repair site. Developing this implantable sensor will pave the way for integrating diagnostics with therapeutics for surgical interventions. The final deliverable at the completion of this proposal will be to have the manufacturing specifications, source material specifications, sizing limits, testing and release specifications for 3D bioprinted nerve conduits with wireless sensing to support a pre-submission meeting with FDA followed by a 510(k) filing.

项目摘要 由于创伤、肿瘤或其他医疗条件造成的周围神经损伤，需要50,000-200,000 每年进行手术，并可能导致完全或部分瘫痪。自体移植是目前的“黄金标准”。 但需要额外的程序来收获移植物，在儿科人群中进行可能是具有挑战性的， 并经常导致供体部位神经瘤的形成和功能丧失。该项目的目标是验证 制备临床前三维聚合物神经导管的材料和方法 嵌入式无线传感器，用于持续监测婴儿/儿童的功能恢复。这个 3D打印的可血管化神经管道模拟神经组织的微结构，嵌入 用于现场监测的无线传感器，并可执行仿生功能以增强神经再生 治疗。目前，还没有临床解决方案来监测神经移植治疗后的成功 做手术。具体目标1将专注于优化3D生物打印神经导管的制造和性能 用于临床翻译的商业级生物材料。为了实现这一目标，我们将使用一个 快速投影、图像引导、直接打印(快速)平台，可以3D打印整个神经导管 只需几秒钟，并将与患者的特定尺寸和形状相匹配。管道将具有线性微通道 沿长度方向为轴突生长，侧边微孔为血管化。特定目标2将验证生成 基于体积缺陷的儿科患者专用导管的数量。为此，我们将协调收集 出生至18岁且有周围神经损伤的儿童患者的MRI资料 累及头部和颈部、上肢和下肢。基于收集的、个性化的MRI数据 将对儿科神经导管进行3D生物打印，以验证快速系统并为计划的 FDA监管审查。特定目标3将开发一种无线供电和控制的传感器来检测 穿过神经缺陷的电脉冲。在这个目标中，我们将通过聚合袖带设计来连接无线传感器 在损伤的小鼠坐骨神经远端观察神经纤维的生长速度和稳定性 穿过治疗性修复现场。开发这种植入式传感器将为集成 用于外科干预的诊断学和治疗学。本建议书完成时的最终交付成果 将有制造规格、原料规格、尺寸限制、测试和放行 支持提交前会议的无线传感3D生物打印神经导管规范 FDA紧随其后的是510(K)fiLING。