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Tissue engineering has recently seen great advancements in many medical fields, including peripheral nerve reconstruction. In the rat median nerve model, we investigated nerve repair by means of bioengineered tissue scaffolds (muscle-vein-combined tubes) focusing on changes in the neuregulin-1/ErbB-receptor system which represents one of the main regulatory systems of axo-glial interaction in peripheral nerves. Repaired nerves were withdrawn at 5, 15, and 30 days postoperative and processed for morphological and retro-transcriptase polymerase chain reaction (RT-PCR) analysis. Results revealed an early and progressive increase in the expression of NRG1α isoform only, while the appearance of the β isoform of NRG1, which is normally present in peripheral nerves, was delayed. In regards to ErbB2 and ErbB3 receptors, their expression increased progressively inside the muscle-vein-combined scaffolds, though with different kinetics. Taken together, these results suggest that variations in neuregulin-1/ErbB system activation play a key role in peripheral nerve regeneration along bioengineered muscle-vein-combined scaffolds. Since similar variations are also detectable in denervated skeletal muscles, it can be hypothesized that the existence of a NRG1's autocrine/paracrine trophic loop shared by both glial and muscle fibers could be responsible for the effectiveness of muscle-vein-combined conduits for repairing nerve defects.