Fabrication of Seamless Electrospun Collagen/PLGA Conduits Whose Walls Comprise Highly Longitudinal Aligned Nanofibers for Nerve Regeneration

An ideal nerve scaffold should supply structural guidance and trophic support to facilitate nerve regeneration. Aligned electrospun nanofibers have shown considerable promise for the precise guidance of regenerating axons in vitro and in vivo. Therefore, uniaxially aligned three-dimension (3D) nanofiberous scaffolds may allow regenerating axons to traverse large gaps to treat severe nerve injuries. However, the aligned 3D conduit was always rolled by an aligned 2-dimensional (2D) sheet in current fabrication methods, which was inconvenient for transplant due to the discontinuous joint and inconsistent size. We developed a modified one-step electrospinning technique to produce a seamless 3D nanofiberous nerve conduit (NC) with highly longitudinal aligned nanofibers that combines the biocompatibility of natural collagen and the strength of the synthetic polymer poly(lactic-co-glycolic acid) (PLGA). Scanning electron microscopy (SEM) confirmed the parallel alignment of the scaffold fibers. To test the effectiveness of these scaffolds at restoring neuronal connections, they were implanted into adult rats across a 13 mm sciatic nerve defect. Tests of motor function, nerve conduction, axonal and Schwann cell morphology, and marker expression all revealed that uniaxially aligned seamless 3D electrospun collagen/PLGA NCs were superior to randomly oriented NCs and inferior to autografts for promoting axon regeneration, myelination, action potential propagation, neuromuscular transmission, and functional recovery. These uniaxially aligned seamless 3D electrospun collagen/PLGA nerve guides can also incorporate signaling molecules and additional structural cues to guide nerve growth, and so may be a promising substitute for autogenous nerve grafts.