Abstract
An innovative technique combining capillary force lithography and phase separation method in one step is applied to fabricate artificial nerve guidance conduit (NGC) for peripheral nerve regeneration. Biodegradable porous, patterned NGC (PP-NGC) using poly(lactic-co-glycolic acid) is fabricated. It has micro-grooves and microporosity on the inner surface to promote axonal outgrowth and to enhance permeability for nutrient exchange. In this study, it is confirmed that the inner surface of micro-grooves can modulate neurite orientation and length of mouse neural stem cell compared to porous flat NGC (PF-NGC) in vitro. Coating with 3,4-dihydroxy-l-phenylalanine (DOPA) facilitates the hydrophilic inner surface of PF- and PP-NGCs via bioinspired catechol chemistry. For in vivo study, PF-NGC and PP-NGC coated with or without DOPA are implanted in the 10 mm sciatic nerve defect margins between proximal and distal nerves in rats. Especially, PP-NGC coated with DOPA shows higher sciatic function index score, onset-to-peak amplitude, and muscle fiber diameter compared to other groups. The proposed hybrid-structured NGC not only can serve as a design for functional NGC without growth factor but also can be used in clinical application for peripheral nerve regeneration.
Keywords 3,4-dihydroxy-l-phenylalanine, microporosity, nerve-guidance porous conduit, sciatic nerve regeneration, topographical cue