Advances in neural interfacing technology are required to enable natural, thought-driven control of a prosthetic limb. Here, we describe a regenerative electrode design in which a polymer-based thin-film electrode array is integrated within a thin-film sheet of aligned nanofibers, such that axons regenerating from a transected peripheral nerve are topographically guided across the electrode recording sites. Cultures of dorsal root ganglia were used to explore design parameters leading to cellular migration and neurite extension across the nanofiber/electrode array boundary. Regenerative scaffold electrodes (RSEs) were subsequently fabricated and implanted across rat tibial nerve gaps to evaluate device recording capabilities and influence on nerve regeneration. In 20 of these animals, regeneration was compared between a conventional nerve gap model and an amputation model. Characteristic shaping of regenerated nerve morphology around the embedded electrode array was observed in both groups, and regenerated axon profile counts were similar at the eight week end point. Implanted RSEs recorded evoked neural activity in all of these cases, and also in separate implantations lasting up to five months. These results demonstrate that nanofiber-based topographic cues within a regenerative electrode can influence nerve regeneration, to the potential benefit of a peripheral nerve interface suitable for limb amputees.