Each year, over 200,000 people in the United States are treated for peripheral nerve injuries requiring surgery. Several nerve guidance conduits (NGCs) have been approved by the FDA, however, when used to repair critical size defects, regeneration results in limited functional recovery and poor quality. Therefore, a conduit fabricated from a material encouraging regeneration, specifically enhancing neurite outgrowth and functional recovery is required. Tyrosine-derived polycarbonates (TyrPCs) are biodegradable and biocompatible polymers offering a unique chemistry that allows for the optimization of their chemical, mechanical, and cellular properties for a specific application. These materials have been used in several medical devices and are effective at supporting neurite outgrowth in vitro. Additionally, peptide mimics of HNK-1 elucidated by the Schachner laboratory show significant promise when used in soluble form within conduits used to treat short defects. For critical size defects, soluble HNK-1 may not suffice; the mimic may diffuse away from the injury site. Thus, the goal of this research was twofold: 1) to develop a TyrPC NGC to treat critical size nerve defects and 2) to establish alternative methods of HNK-1 delivery. Three methods were explored: a collagen hydrogel filler grafted with HNK-1 (developed and provided by the Shreiber laboratory), the secretion of HNK-1 from genetically engineered stem cells, and slow release of HNK-1 from the NGC outer walls. TyrPC was compared to commercially available polyethylene in vitro and conduits fabricated from both materials were evaluated in the mouse femoral nerve model. In vitro results indicated greater protein adsorption and neurite outgrowth on TyrPC as compared to polyethylene. In vivo results showed improved functional recovery and quality of nerve regeneration in animals treated with TyrPC and suggested greater Schwann cell presence and fibrin matrix formation. Furthermore, in vitro results confirmed usefulness of 2 new methods for HNK-1 delivery, release from stem cells and the NGC itself. In vivo studies demonstrated that the influence of a collagen hydrogel with and without HNK-1 depends upon the TyrPC nerve conduit structure: whether or not the conduit was porous. In conclusion, conduits fabricated from TyrPC offer the potential for treatment of critical size nerve gaps.