In contrast to isotropic morphologies of synthetic hydrogels, many biological tissues possess anisotropic hierarchical morphologies leading to extraordinary mechanical properties that cannot be mimicked by synthetic materials. Here, we report preparation of anisotropic silk fibroin cryogels and scaffolds exhibiting a Young's modulus in the range of MPa that sustain up to 20 MPa compressive stresses. The cryogels were prepared by a combined directional freezing - cryogelation process starting from an aqueous 4.2 wt% fibroin solution containing butanediol diglycidyl ether cross-linker and N,N,N',N'-tetramethylethylenediamine. In the first step, the reactor containing the aqueous solution of fibroin, cross linker, and TEMED was immersed into liquid nitrogen at a controlled rate to create a directionally frozen ice template. In the second step, cryogelation reactions were conducted in this frozen solution at -18 degrees C whereby the cryo-concentrated fibroin in the unfrozen microzones of the reaction system forms a 3D fibroin network. The scaffolds exhibit anisotropic microstructure and hence anisotropic mechanical properties, e.g., the Young's modulus is 3.4 +/- 0.5 MPa and 0.8 +/- 03 MPa when measured along the directions parallel and vertical to the freezing direction, respectively. All the cryogels could completely be compressed due to squeezing out of water from their pores. Upon removal of the load, the compressed cryogels immediately recover their original dimensions and mechanical properties by absorbing the released water into their pores. (C) 2017 Elsevier Ltd. All rights reserved.