Abstract: Articles and methods for stem cell differentiation are generally described. In some embodiments, an article for stem cell differentiation may comprise an oxygen permeable substrate having at least a portion of a surface coated with a matrix. The matrix may allow the surface chemistry of the substrate to be altered, such that the cell-substrate surface interactions may be finely controlled without substantially affecting the oxygen permeability of the substrate. The surface chemistry may be altered to promote directed stem cell differentiation by, e.g., modification of the matrix surface with a specific density of biological molecules. In some embodiments, methods for stem cell differentiation may comprise directing the differentiation of stem cells on the articles, described herein, under suitable environmental conditions.