title: Matrix interactions modulate neurotrophin-mediated neurite outgrowth and pathfinding.
abstract: Both matrix biochemistry and neurotrophic factors are known to modulate neurite outgrowth and pathfinding; however, the interplay between these two factors is less studied. While previous work has shown that the biochemical identity of the matrix can alter the outgrowth of neurites in response to neurotrophins, the importance of the concentration of cell-adhesive ligands is unknown. Using engineered elastin-like protein matrices, we recently demonstrated a synergistic effect between matrix-bound cell-adhesive ligand density and soluble nerve growth factor treatment on neurite outgrowth from dorsal root ganglia. This synergism was mediated by Schwann cell-neurite contact through L1CAM. Cell-adhesive ligand density was also shown to alter the pathfinding behavior of dorsal root ganglion neurites in response to a gradient of nerve growth factor. While more cell-adhesive matrices promoted neurite outgrowth, less cell-adhesive matrices promoted more faithful neurite pathfinding. These studies emphasize the importance of considering both matrix biochemistry and neurotrophic factors when designing biomaterials for peripheral nerve regeneration.
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Madl
authors.affiliation: Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Heilshorn
keywords: L1CAM; biomaterials; cell-adhesive ligands; dorsal root ganglia; elastin-like proteins; nerve growth factor; neurotrophic factors