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

项目摘要/摘要 由于创伤、疾病或手术需要引起的神经损伤，通常会导致永久性的 部分或全部功能由受损的神经调节。每年有50,000例周围神经手术 美国是一年，整个欧洲是30万。在完全切断神经后，最佳的临床 神经修复的过程仍然是手术将受伤的神经端到端重新连接，使两端对齐。 尽可能地接近他们原来的对位，并且没有紧张。这种方法提供了最好的 高效有效的轴突再生和功能恢复的可能性。对于存在以下情况的情况 损伤导致的间隙太长，无法进行无张力的端到端修复，使用神经移植物来支持 轴突的再生。移植物的功能恢复程度随着 增加其中一个/两者的间隙长度和从损伤到靶组织的距离。治疗方法可以 提高轴突生长的数量、生长速度和所能跨越的间隙长度 需要的。学术界的PI已经确定了一组显著和临床上- 有意义地增强了这些特性中的每一个，并可以封装在聚合物微珠中，以实现 与移植物结合，可延长释放时间。学术界的PI已经证明了这一点的有效性 系统在一个大型动物模型中。该项目旨在开发生长因子的制造程序。 可用于临床的神经导管移植。这些目标包括 对制作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 这是确定实验室验证技术的商业可行性所必需的。

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.