Semi-synthetic hydrogel composition and stiffness regulate neuronal morphogenesis.

This study describes the use of a set of protein-based biomaterials that allow us to explore the mechanism of cell-mediated 3-D invasion associated with peripheral nerve regeneration. Hydrogels made from poly(ethylene glycol) (PEG) conjugated extracellular matrix proteins, including fibrinogen, gelatin and albumin were compared in their ability to support the neurite extension and glial cell migration from dorsal root ganglion (DRG) as compared to PEG only hydrogel controls. The synthetic polymer in the system provides a cross-linked network with controlled mechanical properties and degradation, whereas the protein components provide the unique extracellular matrix (ECM) for controlling neuronal cell morphogenesis. A range of hydrogel compositions were found to support DRG cell outgrowth, based on the mechanical properties, density and proteolytic degradation of the matrix. The 3-D invasion and morphogenesis of newly grown neurites and glial cells in the different materials were characterized and correlated to the properties of the scaffolds. The DRG cell outgrowth was highly correlated with the density of different hydrogel compositions.