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.

项目总结