Functional Evaluation of a 3‐D Nerve Construct Utilized for Repair of a Critical Nerve Defect

Abstract

Nerve grafts are often required to replace tissue damaged by disease, surgery, or extensive trauma. Limitations associated with grafting such as graft availability, donor site morbidity, and immune rejection have led investigators to develop strategies to engineer nerve tissue. The purpose of our research was to engineer a scaffold‐less 3‐D engineered nerve construct that would be functionally equivalent to native nerve. As per our labs' previously established protocol, fibroblasts isolated from F344 rat Achilles tendon and neural cells from E15 fetal spinal cords were co‐cultured and engineered into 3‐D constructs. Following 3‐D formation, neural cells oriented along the axis of strain. The functionality of a nerve is measured by its ability to conduct an electrical signal along the length of the cell axon or nerve conduction velocity. To establish an in vivo standard, conduction velocities were measured in neonatal rats ranging from 7 – 28 days. The in vivo velocities peaked at 28 days when recordings reached the expected adult conduction velocity of 16 m/s. One week after establishing a 3‐D conformation, nerve constructs were utilized in a 2 cm nerve defect repair. Following a 2 month recovery, conduction velocities and target muscle mechanical properties were evaluated. Our results suggest that our scaffold‐less 3‐D engineered nerve construct may be a viable strategy for nerve repair. Supported by R01 AR054778‐02 and gift from the Barbara & Richard Raynor Medical Foundation.