Congenital absence or injury to peripheral nerves yields devastating consequences. The gold standard for nerve gap repair comprises nerve autografting, wherein noncritical nerves are harvested for use in guiding regeneration of more important nerves towards a distal target. Limitations of nerve autografting are many, and include sensory loss with potential for chronic pain development at the donor site. There is a critical need for bioengineered devices that circumvent requisite use of nerve autografts and their associated morbidity. Our long-term goal is to employ emerging gene therapy and bioengineering techniques to bring to market an off-the-shelf bioengineered nerve guidance conduit (NGC) whose clinical performance rivals that of nerve autografts over short and long-distances. Our central hypothesis is that viral vectors may be incorporated within NGCs to induce local expression of growth factors that enhance neural regeneration. In Aim 1, we will develop a double-labelled fluorescent reporter murine model for high-throughput quantification of Schwann cell and axonal ingrowth across nerve gaps. In Aim 2, we will evaluate the ability of transgenes packaged within various viral vectors to be delivered and expressed within NGCs bridging a murine sciatic nerve defect. If successful, this work would establish a novel means for biological functionalization of NGCs, circumventing the cost and complexity of exogenous growth factor and live cell incorporation, while heralding a paradigm shift in their design. If successful, this research would lay the foundation for development of high-performance bioengineered alternatives to nerve autografts, carrying potential to reduce morbidity and enhance outcomes among children undergoing interposition grafting of peripheral nerves.