Controlled Gradient Release of Biologics: Enhanced Nerve Conduit for Long‐Gap Injury Repair

生物制剂的受控梯度释放：增强神经导管以修复长间隙损伤

• 批准号: 10603563
• 负责人: Mario Ignacio Romero-Ortega
• 金额: $ 42.2万
• 依托单位: PIONEER NEUROTECH INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10603563
• 关键词: Acceleration; Acute; Affect; Afferent Neurons; Allografting; Animal Model; Autologous; Autologous Transplantation; Axon; Biological; Biological Products; Cell Proliferation; Characteristics; Clinical; Conditioned Culture Media; Data; Detection; Devices; Disease; Distal; Encapsulated; Enzyme-Linked Immunosorbent Assay; Europe; FDA approved; Fluorescence; Goals; Growth; Growth Factor; Histologic; Housing; Iatrogenesis; Image; In Vitro; Injury; Laboratories; Lead; Legal patent; Length; Mediating; Methods; Microfluidics; Muscle; Natural regeneration; Nerve; Nerve Regeneration; Neuregulins; Neuroma; Operative Surgical Procedures; Pain; Patients; Peripheral; Peripheral Nerves; Phase; Polyglycolic Acid; Polymers; Procedures; Process; Proliferating; Rattus; Recovery; Recovery of Function; Regenerative capacity; Reproducibility; Resources; Role; Sampling; Schwann Cells; Sensory; Sepharose; Skin; Small Business Technology Transfer Research; Specific qualifier value; Speed; Spinal Ganglia; Structure; Surface; Surgeon; System; Techniques; Technology; Testing; Time; Tissues; Trauma; United States; Universities; Visualization; Work; axon growth; axon regeneration; comorbidity; fabrication; implantable device; improved; in vivo; injury and repair; innovation; loss of function; migration; motor recovery; myelination; nerve autograft; nerve gap; nerve injury; nerve repair; neurotrophic factor; particle; peripheral nerve repair; poly(lactic acid); postnatal; regenerative; release factor; remyelination; repaired; response to injury; sciatic nerve; success

Project Summary / Abstract Nerve injuries arising from trauma, disease, or as a surgical necessity, lead most often to permanent loss of some or all functions mediated by the injured nerves. 50,000 peripheral nerve procedures are performed every year in the US, and 300,000 across Europe. After complete transection of a nerve, the optimal clinical procedure for nerve repair remains the surgical end-to-end reattachment of the injured nerve, aligning the ends into as close to their original apposition as possible and without tension. This approach offers the best possibility for efficient and effective axonal regeneration and functional recovery. For cases in which there is damage that results in a gap that is too long for tensionless end-to-end repair, nerve grafts are used to support the regeneration of axons. The degree of recovery of function with grafts decreases precipitously with increases in either/both gap-length and the distance from the injury to the target tissues. Treatments that can enhance the number of axons growing, the speed of their growth, and the gap-length they can span are needed. The academic PI has identified a combination of growth factors that significantly and clinically- meaningfully enhances each of these characteristics and can be encapsulated in polymer beads to enable incorporation into grafts for extended-duration of release. The academic PI has demonstrated efficacy of this system in a large animal model. This project aims to develop the fabrication procedures for growth factor encapsulation and impregnation into nerve conduit grafts that could be used clinically. The goals include in vitro and in vivo assessment of the fabricated grafts to validate that they remain effective. This work is necessary to determine the commercial viability of the lab-proven technology.

项目摘要 /摘要 创伤，疾病或外科手术必要性引起的神经损伤，最常见的是永久丧失 受伤神经介导的一些或所有功能。每次执行50,000个外围神经手术 在美国一年，欧洲有30万。完全横断神经后，最佳临床 神经修复的过程仍然是受伤神经的手术端到端重新介绍，使末端对齐 尽可能接近其原始同名，而无需紧张。这种方法提供了最好的 有效有效的轴突再生和功能恢复的可能性。对于有 损害导致间隙太长，无法进行无张力的端到端修复，使用神经移植物来支撑 轴突的再生。用移植物的功能恢复程度随着 间隙长度和从损伤到目标组织的距离增加。可以 增强轴突的生长数量，其生长速度以及它们可以跨越的间隙是 需要。学术PI已经确定了多种增长因素的组合，这些因素在临床上显着和临床 有意义地增强了这些特征中的每一个，并且可以封装在聚合物珠中以启用 掺入移植物中以扩展释放。学术PI已经证明了这一点 大型动物模型中的系统。该项目旨在开发生长因子的制造程序 可以在临床上使用的神经导管移植物的封装和浸没。目标包括 体外和体内评估制造的移植物，以验证它们保持有效。这项工作是 确定实验室预处理技术的商业生存能力所必需的。