Collagen-based scaffold micropatterning to induce morphogenetic pathways regulation in adult nerve regeneration

Peripheral nervous system injury is a frequent traumatic event, affecting a growing field of population, according to the change in lifestyle. Nerve autograph is still the golden standard, however it is invasive and limited in terms of amount and dimension of the available source. Various alternative therapeutic approaches have been proposed and results have been, so far, inconsistent, in terms of both quality and extent of nerve regeneration and re-innervation. Here, a novel technique is presented able to produce tubular collagen-based scaffolds, characterized by a radially/axially patterned microporosity (MPCS). The process has been modelled by means of the Lamm differential equation, according to appropriate scaling laws. In the present investigation, we tested in vivo the clinico-pathological impact of this MPCS over a 10-mm critical size defects in the adult rat sciatic nerve. Rats with transection of the sciatic nerve and implanted with either commercial collagen or silicon conduits were used as controls. MPCS-implanted rats showed significantly improved nerve regeneration at both neurophysiological and neuropathological levels, as compared to control rats. Our data demonstrate that this specific tubular scaffold micro-patterning orchestrates physiological regeneration in the adult rat sciatic nerve over a 10-mm critical size defect. Indeed, whole genome gene expression analyses confirm that the MPCS induces selective gene expression patterns and enhanced cells proliferation, motility and myelination, with a remarkable cell-instructing behavior. The development of morphogenesis phenomena during nerve regeneration process opens new perspectives towards the clinical application of MPCS in this field, owing to its ease of production, cost-effectiveness, favorable degradation rate and remarkable cell-instructing behavior.