In recent tissue engineering field, it is being reported that the fabrication of 3D scaffolds having high porous and controlled internal/external architectures can give potential contributions in cell adhesion, proliferation and differentiation. To fabricate these scaffolds, various solid free-form fabrication technologies are being applied. The solid free-form fabrication technology has made it possible to fabricate solid free-form 3D microstructures in layer-by-layer manner. In this research, we developed a multi-head deposition system (MHDS) and used design of experiment (DOE) to fabricate 3D scaffold having an optimized internal/external shape. Through the organization of experimental approach using DOE, the fabrication process of scaffold, which is composed of blended poly-caprolactone (PCL), poly-lactic-co-glycolic acid (PLGA) and tricalcium phosphate (TCP), is established to get uniform line width, line height and porosity efficiently. Moreover, the feasibility of application to the tissue engineering of MHDS is demonstrated by human bone marrow stromal cells (hBMSCs) proliferation test.