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.

项目总结/摘要 由创伤、疾病或作为手术必需品引起的神经损伤，最常导致永久性神经功能丧失。 损伤神经介导的部分或全部功能。每年有5万例外周神经手术 美国一年，欧洲30万。在完全切断神经后， 神经修复的过程仍然是损伤神经的外科端对端再连接， 尽可能地接近它们原来的并置而不产生张力。这种方法提供了最好的 可能性的高效和有效的轴突再生和功能恢复。对于那些 损伤导致的间隙太长，无法进行无张力端对端修复，神经移植物用于支持 轴突的再生移植物的功能恢复程度随着时间的推移而急剧下降。 间隙长度和从损伤到靶组织的距离之一/两者增加。治疗方法可以 增加轴突生长的数量，它们的生长速度，以及它们可以跨越的间隙长度， needed.学术PI已经确定了一个生长因子的组合，显着和临床- 有意义地增强了这些特性中的每一个，并且可以包封在聚合物珠粒中， 结合到移植物中以延长释放的持续时间。学术PI已经证明了这一点的有效性 在大型动物模型中。本项目旨在开发生长因子的制备工艺 包封和浸渍到可用于临床的神经导管移植物中。目标包括在 对所制造的移植物进行体外和体内评估，以验证它们仍然有效。这项工作是 确定实验室证明的技术的商业可行性所必需的。