The project goal is to design nerve conduits with an optimal architecture to successfully achieve complete nerve repair. Indeed, though millions of people suffer from peripheral nerve injuries annually, today's golden standard techniques do not guarantee full recovery, especially if the nerve damage encompasses large gaps. The challenge is to design nerve conduits with an interior that mimics the natural nerve architecture, as to optimally facilitate nerve regeneration and to guide growing axons from one side to the other. Therefore, the new technique of yarn electrospinning is used in this project, as it enables longitudinal, aligned nanofibrous structures (nanoyarns) which mimic the nerves’ fibrous nature in dimension and morphology. The nerve conduit design includes the eco-friendly, continuous production of individual, biocompatible and biodegradable poly(e-caprolactone) nanoyarns after which they are bundled with a protective, flexible, biocompatible nanofibrous shell. A range of innovative methodologies is studied to produce and incorporate cell degradable nanofibers and biological cues in the nerve conduit, with the ultimate goal to precisely tune the conduit's architecture as to result in efficient nerve regeneration and degradation combined with sufficient mechanical properties. Therefore, each step in the scaffold design is assessed by combining a profound material characterisation and in vitro study with an in vivo analysis of the most optimal conduits.