3-DIMENSIONAL EXTRACELLULAR-MATRIX ENGINEERING IN THE NERVOUS-SYSTEM

Growing neurites are guided through their environment during developme nt and regeneration via different cellular and extracellular matrix (E CM) molecular cues. To mimic cell-matrix interactions, a three-dimensi onal (3D) hydrogel-based ECM equivalent containing a covalently immobi lized laminin oligopeptide sequence was designed to facilitate nerve r egeneration. This study illustrates that the oligopeptide domain CDPGY IGSR covalently linked to an agarose gel as a bioartificial 3D substra te successfully supports neurite outgrowth from dorsal root ganglia (D RG) in vitro. The specificity of the neurite promoting activity was il lustrated through the inhibition of neurite outgrowth from DRG in a CD PGYIGSR-derivatized gel in the presence of solubilized CDPGYIGSR pepti de. Gels derivatized with CDPGYIGSK and CDPGRGSYI peptides stimulated a smaller increase of neurite outgrowth. In vivo experiments revealed the capability of a CDPGYIGSR-derivatized gel to enhance nerve regener ation in a transected rat dorsal root model compared to an underivatiz ed gel, a CDPGRGSYI gel, and saline-filled nerve guidance channels. Th ese data suggest the feasibility of a 3D hydrogel-based ECM equivalent capable of enhancing neurite outgrowth in vitro and in vivo. (C) 1998 John Wiley & Sons, Inc.