Alginate (ALG) hydrogels incorporating vascular endothelial growth factor (VEGF) were nano-coated with polyelectrolyte multilayer (PEM) films composed of chitosan (CT) and dextran sulfate (DEX) in order to control the VEGF release from the hydrogels. When non- and nano-coated ALG hydrogels containing VEGF were incubated in phosphate-buffered saline (PBS) at 37 degrees C for the prescribed times, the nano-coated hydrogels were stable, even after incubation for a week, whereas the non-coated hydrogels collapsed after 6 h. The release profile of VEGF from the non- and nano-coated ALG hydrogels was evaluated by an enzyme-linked immunosorbent assay (ELISA). Although all of the VEGF incorporated into the non-coated ALG hydrogels was released within 6 h by the collapse, only a few percent of the VEGF incorporated in the nano-coated hydrogels was released. Furthermore, the incorporated VEGF in the nano-coated hydrogels was released continuously, even after a month, without any initial burst release. The release percentage of VEGF was easily controlled by the PEM film thickness on the surface of the ALG hydrogels. The VEGF released from the nano-coated hydrogels retained its activity without denaturation. Consequently, the nano-coating of hydrogel surfaces with PEM films may be useful for controlled and sustained drug-delivery systems.