The present invention relates to scaffolds that can physically guide cells, e.g. neurons, while best matching the material properties of native tissue. The present invention also relates to methods of generating such scaffolds, and for the use of such scaffolds, e.g. in spinal cord and peripheral nerve injury repair. The methods of the present invention include a uniquely controlled freeze casting process to generate highly porous, linearly oriented scaffolds. The scaffolds of the present invention not only comprise a highly aligned porosity, but also contain secondary guidance structures in the form of ridges running parallel to the pores to create a series of microstructured and highly aligned channels. This hierarchy of structural guidance aligns and guides neurite outgrowth down the channels created by the ridges, and keep neurites from branching perpendicular to the inter-ridge grooves.