Tissue engineered scaffolds must have an organized and repeatable microstructure which enables cells to assemble in an ordered matrix that allows adequate nutriental perfusion. In this work, to evaluate the reciprocal cell interactions of endothelial and osteoblast-like cells, human osteoblast-like cells (MG63) and Human Umbilical Vein Endothelial Cells (HUVEC) were co-seeded onto 3D geometrically controlled porous poly(ε-caprolactone) (PCL) and cultured by means of a rotary cell culture system (RCCS-4DQ). In our dynamic co-culture system, the lack of significant enhancement of osteoblast ALP activity and ECM production indicated that the microgravity conditions of the rotary system affected the cells by favoring their proliferation and cellular cross-talk. These results emphasize how osteoblasts increase endothelial cell proliferate and endothelial cells amplify the growth of osteoblasts but decrease their differentiation. This dynamic seeding of osteoblasts and endothelial cells onto a 3D polymeric scaffold may represent a unique approach for studying the mechanisms of interaction of endothelial and osteoblast cells as well as achieve a functional hybrid in which angiogenesis, furnished by neo-vascular organization of endothelial cells may further support osteoblasts growth. Furthermore, this in vitro model may be useful in examining the applicability of novel material structures for tissue engineering.