Creating three-dimensional biochemical channels in a degradable matrix for nerve regeneration.

摘要

The purpose of this study was to create a biodegradable nerve guidance matrix consisting of three-dimensional cell-adhesive, glycine-arginine-glycine-aspartic acid-serine (GRGDS) biochemical channels, separated by non-adhesive volumes. This was done using ultraviolet laser micropatterning of a hyaluronic acid hydrogel matrix, which was modified with thiol groups protected by the photolabile 2-nitrobenzyl moiety. Using a focused laser, the 2-nitrobenzyl group was cleaved, exposing reactive thiol groups along its path, which were then reacted with maleimide-functionalized GRGDS. Peptide modification was confirmed using fluorescently-labelled peptides, and analysis of the fluorescence intensity profile showed bidirectional concentration gradients within the channels. Rheological characterization showed that UV irradiation did not significantly affect the mechanical strength of the matrix. Neural cells cultured on the channel-modified hyaluronic acid matrices preferentially extended neurites towards the GRGDS channels relative to scrambled GRGDS controls. Such a matrix may be used as a bridge to enhance axonal regeneration in nerve regenerative devices.