Incorporation of parallel electrospun fibers for improved topographical guidance in 3D nerve guides

Abstract

Three dimensional (3D) conduits facilitate nerve regeneration. Parallel microfibers have been shown to guide axon extension and Schwann cell migration on flat sheets via topographical cues. However, incorporation of aligned microfibers into 3D conduits to accelerate nerve regeneration has proven challenging. We report an electrospinning technique to incorporate parallel microfibers into 3D constructs at high surface areas while retaining an open architecture. The nerve guide consists of many microchannels lined with a thin layer of longitudinally-aligned microfibers. This design aims to maximize benefits of topographical cues without inhibiting cellular infiltration. We support this hypothesis by demonstrating efficient cell infiltration in vitro. Additionally, this new technique reduces wall thickness compared to our previous design, providing a greater total area for tissue growth. This approach results in an architecture that very closely mimics the structure of decellularized nerve but with larger microchannel diameters to encourage cell infiltration. We believe that reproducing the native architecture is the first step toward matching autograph efficacy. Furthermore, this design can be combined with other biochemical cues to promote nerve regeneration.