The aim of this study was the design of bi-modal porous scaffolds for bone tissue engineering (bTE) by combining supercritical CO2 (scCO(2)) foaming and porogen leaching techniques. Poly(epsilon-caprolactone) (PCL) was melt blended with thermoplastic zein (TZ) w/o the addition of 20 wt.% of HA particles to prepare a 40/60 (w/w) co-continuous blend and a 32/48/20 multi-phase composite, respectively. The materials were subsequently gas foamed by using scCO(2) as blowing agent. Saturation and foaming temperatures and pressures, as well as depressurization time were selected in order to optimize the pore structure of the foams and, to induce the formation of a macro-porosity suitable for bone cell adhesion and colonization. The foams were subsequently soaked in water in order to leach out the plasticizer from the TZ phase and, to induce the formation of a bi-modal pore structure. The effect of the composition of the materials and the foaming parameters on the properties of the scaffolds was assessed by SEM, image analyses and static compression tests. Furthermore, in vitro cell cultures were performed by using MG63 osteoblasts to assess the biocompatibility of the scaffolds and, to evaluate their capacity to promote cell adhesion, colonization and proliferation. The results of this study demonstrated that the proposed technique allowed for the design and fabrication of bi-modal porous PCL/TZ and PCL/TZ-HA composite scaffolds by a green process. In particular, the scaffolds showed a 20-400 mu m macro-porosity, obtained by performing the scCO(2) foaming process at a temperature higher than PCL melting, coupled with a 3 mu m micro-porosity, obtained by leaching out the plasticizer from the TZ phase. Finally, the biological characterization demonstrated that the scaffolds allowed cell adhesion, colonization and proliferation up to 28 days of in vitro culture, therefore demonstrating potential for bTE. (C) 2012 Elsevier B.V. All rights reserved.