Limitations in current nerve regeneration techniques have stimulated the development of various approaches to mimic the extrinsic cues available in the natural nerve regeneration environment. We are developing several biomaterials approaches to modulate the microenvironment of a regenerating nerve through tailored presentation of signaling molecules, creating physical and biochemical guidance cues to direct axonal regrowth across nerve lesion sites. These approaches include cell-based strategies based on increasing the neurotrophic support, adhesion guidance and myelination capacity of Schwann cells and other alternative cell types to enhance nerve regrowth and functional recovery. In addition, presenting directional guidance cues in nerve guidance conduits could improve the regenerative outcomes of cell delivery. These platforms provide inspirations to engineering the next generation of nerve repair solutions.