The hydrophobic nature and the regular scaffold architecture of bioplotted poly(epsilon-caprolactone) (PCL) scaffolds present some hurdles for homogeneous tissue formation and differentiation. The current hypothesis is that a synergistic effect of applied surface modification and scaffold design enhances colonization and osteogenic differentiation. First, PCL scaffolds with a 0/90 degrees lay-down pattern (0/90) were plotted and subjected to an oxygen plasma (O-2) or multistep surface modification, including post-argon 2-amino-ethylmethacrylate grafting (AEMA), followed by immobilization of gelatin type B (gelB) and physisorption of fibronectin (gelB Fn). Secondly, scaffolds of different designs were plotted (0/90 degrees shift (0/90 S), 0/45 degrees and 0/90 degrees with narrow pores (0/90 NP)) and subjected to the double protein coating. Pre-osteoblasts were cultured on the scaffolds and the seeding efficiency, colonization and differentiation were studied. The data revealed that a biomimetic surface modification improved colonization (gelB Fn > gelB > AEMA > O-2). Compact scaffold architectures (0/90 NP, 0/45, 0/90 S >0/90) positively influenced the seeding efficiency and differentiation. Interestingly, the applied surface modification had a greater impact on colonization than the scaffold design. In conclusion, the combination of a double protein coating with a compact design enhances tissue formation in the plotted PCL scaffolds. (C) 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.