Abstract

Various therapeutic approaches are applied to patients suffering from peripheral nerve injuries with only partial success so far, in terms of both quality as well as extent of regeneration and re-innervation. We have previously developed a micro-patterned collagen scaffold (MPCS) with a peculiar radially aligned porosity of the tube wall, and predicted that its microstructure might play a significant role in the regulation of cellular and molecular mechanisms sustaining cell behaviour inside the scaffold and, in turn, improving distal induced regeneration. Here we tested in vivo the clinico-pathological impact of this MPCS over a 10-mm critical size defects in the adult rat sciatic nerve. Neurophysiological and morphological data demonstrate physiological sciatic nerve regeneration in MPCS -implanted transected rats, as compared to as compared to transected rats implanted with either clinical-grade collagen tubes, or with silicone tubes. Whole genome gene expression analyses confirm MPCS -specific remarkable coordinated induction of clusters of genes responsible for cell proliferation, motility and myelination. We here establish the dynamics of the major cellular and molecular pathways regulating the effects of this novel MPCS on physiological peripheral nerve regeneration. Our findings open new perspectives towards the clinical application of this micropatterned scaffold, owing to its ease of production, cost-effectiveness, favorable degradation rate and remarkable cell-instructing behavior.