The present invention provides compositions and methods for the production of silk fibroin matrices surface-PEGylated on one or more surfaces. Such surface-PEGylated silk fibroin matrices can be used in biomedical applications, such as anti-adhesive and anti-thrombosis materials. Silk matrices may be surface-PEGylated, for example, by a reaction with a functional group-activated PEG. Controlling the degree of PEGylation on surface of silk fibroin matrix can regulate both the degradation rate of the silk matrix, and the differentiated adhesion of cells or differentiated adsorption of proteins on the surface of the silk matrix. The present invention also provides for silk fibroin matrices having one or more surfaces possessing differentiated adhesion properties, which allows for tissue integration on the adherent side and inhibition of tissue adhesion to the opposing tissues or organs. Embedding active agents in silk fibroin matrices provides more benefits, such as promoting tissue ingrowth on the adherent side of the matrix.