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

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.