Hybrid biomedical structures have been used widely in various tissue-regenerating materials because they effectively induce exceptional physical and cellular responses. In this study, a new hybrid process was used to design a three-dimensional (3D) biomedical hybrid scaffold with a controlled pore-structure and high mechanical strength. A melt-dispensing method was used to obtain mechanical properties and electrohydrodynamic direct-jet (EHD-DJ) printing was used to provide microsized fibrous structures for the scaffold. Furthermore, the poly(epsilon-caprolactone) (PCL) hybrid scaffolds were coated biomimetically with type-I collagen to increase bioactive interactions between cells and scaffolds. The fabricated scaffolds showed similar mechanical properties to the two control scaffolds: however, the results of culturing osteoblast-like (MG63) cells showed significant increases in in vitro cellular activities (cell viability > twofold and calcium deposition > sevenfold). Based on these results, we propose a newly designed hybrid scaffold that can support significant in vitro cellular activities at the interface between cells and the 3D micro-pore structure for soft and hard tissue regeneration. (C) 2015 Elsevier Inc. All rights reserved.