Silk fibers have outstanding mechanical properties. These fibers are insoluble in organic solvents and water, are biocompatible, and exhibit slow biodegradation in vitro and in vivo due to the hydrophobic nature of the protein and the presence of a high content of beta-sheet structure. Regenerated silk fibroin can be processed into a variety of materials normally stabilized by the induction of beta-sheet formation through the use of solvents or by physical stretching. To extend the biomaterial utility of silk proteins, options to form water-stable silk-based materials with reduced beta-sheet formation would be desirable. To address this need for more rapidly degradable silk biomaterials, we report the preparation of water-stable films from regenerated silk fibroin solutions, with reduced beta-sheet content. The keys to this process are the preparation of concentrated (8 % by weight) aqueous solutions of fibroin and a subsequent water-based annealing procedure. These new materials degrade more rapidly due to the reduced P-sheet content, as determined in vitro via enzymatic hydrolysis, yet support human adult stem-cell expansion in vitro in a similar or improved fashion to the crystallized proteins in film form. These new silk-based materials extend the range of biomaterial properties that can be generated from this unique family of proteins.