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，肿瘤或其他医疗状况，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麻痹。自体移植是当前的“黄金标准” 但是需要其他程序来收集移植物，可能会挑战在小儿人群中进行的挑战， 并且通常会导致神经瘤形成和供体部位的功能丧失。该项目的目的是验证 制造临床前聚合物三维（3D）神经管道的材料和方法 嵌入式无线传感器，用于连续监测婴儿/儿童使用的功能恢复。这 3D打印的可血管神经导管模仿神经组织的微体系结构，并嵌入 无线传感器进行原位监测，可以执行仿生功能以增强神经再生 疗法。当前，没有临床解决方案来监测神经移植疗法的成功 外科手术。特定目标1将专注于优化3D-生物包裹的神经导管制造和使用 用于临床翻译的商业级生物材料。为了在此目标中制造这样的导管，我们将使用 快速投影，图像引导，直接打印（快速）平台，可以在整个神经导管中3D打印 仅仅几秒钟，将与患者的特定大小和形状相匹配。导管将有线性微通道 沿着轴突生长和侧面微孔的长度进行血管化。特定目标2将验证产生 基于体积缺陷的儿科特异性导管的。在此目标中，我们将协调 从出生到18岁的小儿患者之间的MRI数据，性别和周围神经损伤 涉及头部和颈部，上肢和下肢。根据收集，个性化的MRI数据 小儿神经管道将是3D生物打印的，以验证快速系统，并提供计划的证据 FDA监管审查。特定的AIM 3将开发无线功率和受控的传感器来检测 神经缺陷的电脉冲。在此目标中，我们将通过聚合袖带设计连接无线传感器 到受伤的小鼠坐骨神经的远端，以评估神经纤维生长的速度和鲁棒性 在整个治疗维修部位。开发此植入传感器将为整合铺平道路 通过手术干预的治疗诊断。本提案完成时的最后交付 将具有制造规格，原始材料规格，尺寸限制，测试和释放 具有无线敏感性的3D生物打印神经导管的规格，以支持与与 FDA随后是510（k）填充。