A poly(DL-lactic-co-glycolic acid) (PLGA)sandwiched cell/fibrin construct was fabricated to overcome the weak mechanical properties of cell/hydrogel mixtures. This construct was formed with a step-by-step mold/extraction method to generate a middle smooth muscle layer of natural blood vessels. A desired three-layer construct, as an integrated entity with optimized inner structures, was achieved by the control of the size of the molds, the concentration of the polymer systems, and the temperature of the extraction and polymerization processes. The constructs were fabricated with the following dimensions: length = 10-25 mm, diameter >2 mm, and wall thickness = 0.6-2 mm. Different microstructures in different layers of the sandwiched structure resulted in different functions. The pore structure in the inner PLGA and middle fibrin layers was beneficial for nutrient transference, whereas the solid structure without pores in the outmost surface of the outer PLGA layer could prevent fluid from leaking during in vitro culturing and in vivo implantation. This study showed that this can be a promising approach for the fabrication of synthetic-polymer-sandwiched viable cell/hydrogel constructs for wide potential application in complex organ manufacturing. (C) 2010 Wiley Periodicals, Inc. J Appl Polym Sci 120: 1199-1207, 2011