Rapid prototyping techniques are widely used to fabricate well-defined three-dimensional structures of tissue homologs. The piston-assisted microsyringe (PAM2) is a rapid prototyping technology specifically developed for low-shear stress extrusion of viscous hydrogel solutions containing cells. In this article the working parameters of the system were established to guarantee the realization of spatially controlled hydrogel scaffolds. Moreover the shear stresses acting on the cell membrane during extrusion was investigated through a computational fluid-dynamic analysis. The computational models show that the shear stress on the cells is of the order of 100 Pa during the extrusion process. HepG2 cells encapsulated in alginate were then extruded into spatially organized hepatic lobule-like architectures and their viability and function were evaluated. The results show that the metabolic fingerprint of the cells is preserved with respect to controls and the cells are uniformly distributed through the gel scaffold.