Recently, eco-friendly and biologically harmless products of waterborne polyurethane (WPU) instead of solvent-borne polyurethane have been strongly progressed in both industries and research areas. Accordingly, we developed a WPU-based macroporous sponge as a skin tissue engineering matrix. Also, the WPU dispersion in water was modified by using a foaming agent in order to create creamy emulsion resulting in enlarging surface area wherein cells could adhere, grow, and proliferate. We investigated the effect of a foaming agent on the morphology of surface and internal structure, wettability. In vitro studies also confirmed enhanced adherence and proliferation of cells with increased metabolic rate. These results proved that the use of foaming agent could alter the internal structure, surface property, and biocompatibility.