Homogeneous and bilayered macroporous poly(2-hydroxyethyl methacrylate), p(HEMA), hydrogel scaffolds were examined as possible matrices for nerve regeneration in the CNS. An important issue to consider for a CNS scaffold is that it must be able to closely mimic the natural tissue it is replacing, while remaining intact, and mechanically stable enough to allow for regenerating axons to elongate through it. Phase-separated homogeneous and bilayered p(HEMA) scaffolds were fabricated, by varying water, crosslinking, and initiating agents; all of which directly affected the mechanical properties of the polymer. An increase in water concentration resulted in a decrease in the modulus for a given crosslinking and initiating concentration for all homogenous scaffolds, but the same result was not evident in the bilayered scaffolds. The distinct regions within the bilayered scaffolds generate a matrix, containing both a highly porous region with modulus values representative of spinal cord tissue, as well as a nonporous region that provides overall mechanical stability to the entire implant. The overall result is a composite matrix for possible use in CNS nerve regeneration, which mimics the mechanical properties of spinal tissue, but can withstand the forces that it will be subjected to in the injury site. (c) 2006 Wiley Periodicals, Inc.