| Neurotrophic factors present as concentration gradients are neurotropic cues that direct axonal growth toward their targets. Multiple factors work together to ensure axons reach the proper targets, likely interacting with one another via intracellular signalling pathways. Nerve growth factor (NGF) and neurotrophin-3 (NT-3) are neurotrophins known to guide axons as well as to promote axonal growth following injury to the spinal cord or peripheral nerve. The receptors for these growth factors were shown to be co-localized on E10 chick dorsal root ganglion (DRG) cells, providing an opportunity for synergism. Gradients of NGF and NT-3 were immobilized in a cell-invasive, cell-adhesive scaffold made from 15% poly(2-hydroxyethylmethacrylate) [p(HEMA)]. A minimum NGF concentration gradient of 310ng/ml/mm was required to guide chick DRG neurites, which was consistent with previous results. A lower concentration gradient of 200ng/ml/mm of NGF was shown to elicit guidance when an NT-3 concentration gradient of 200ng/ml/mm was also present, indicating a synergistic response. |
