Potential treatment strategies for the repair of spinal cord injury (SCI) currently favor a combinatorial approach incorporating several factors, including exogenous cell transplantation and biocompatible scaffolds. The use of scaffolds for bridging the gap at the injury site is very appealing although there has been little investigation into the central nervous system neural cell interaction and survival on such scaffolds before implantation. Previously, we demonstrated that aligned microgrooves 12.5-25 μm wide on ε-polycaprolactone (PCL) promoted aligned neurite orientation and supported myelination. In this study, we identify the appropriate substrate and its topographical features required for the design of a three-dimensional scaffold intended for transplantation in SCI. Using an established myelinating culture system of dissociated spinal cord cells, recapitulating many of the features of the intact spinal cord, we demonstrate that astrocytes plated on the topography secrete soluble factors(s) that delay oligodendrocyte differentiation, but do not prevent myelination. However, as myelination does occur after a further 10-12 days in culture, this does not prevent the use of PCL as a scaffold material as part of a combined strategy for the repair of SCI.