Temporary scaffolds can be used as surrogates of the extracellular matrix to favour the regeneration Of tissue and organs. Several techniques have been proposed for scaffolds fabrication; but they have various limitations. Above all, it is very difficult to obtain the coexistence of the macro and microstructural characteristics necessary for a successful application. To overcome these limitations, we tested a new supercritical fluid assisted technique for the formation of 3D scaffolds, that consists of three subprocesses: the formation of a polymeric gel loaded with a solid porogen, the drying of the gel using supercritical CO2 (SC-CO2), the washing with water to eliminate the porogen. We obtained poly(l-lactic acid) (PLLA) scaffolds with elevated porosity (>90%) and interconnectivity, with good mechanical properties (compressive modulus up to 81 kPa). The most innovative characteristic of these scaffolds is the fibrous nanostructure coupled to micronic cells of controllable size. We also produced scaffolds with predetermined shape and size in a short time (<30 h) and without an appreciable solvent residue (<5 ppm). (C) 2008 Elsevier B.V. All rights reserved.