Multifunctional bioactive chemically cross-linked elastin-like polymers (ELPs) have been prepared as three-dimensional scaffolds for tissue engineering. The salt-leaching/gas-foaming technique was found suitable to prepare highly porous biodegradable hydrogels based on this novel material type. The porosity can be controlled by the amount of sodium hydrogen carbonate incorporated during the cross-linking reaction, whereas the mean pore size is determined by the salt particle size. The gas-foaming process, which involves immersion in a citric acid solution after the cross-linking, facilitates pore interconnectivity and allows a grooved surface essential for cell colonization. Due to the thermoresponsive nature of the ELPs, their physical properties are strongly influenced by the temperature of the aqueous medium. The feasibility to obtain tridimensional scaffolds for tissue engineering has been studied by testing the adhesion and spreading of endothelial cells into the porous ELP hydrogels. The methods and structures described herein provide a starting point for the design and synthesis of macroporous multifunctional elastin-like hydrogels with potential broad applicability.