A major question in biomimetic tissue engineering is how much of the structure/function of native vasculature needs to be reproduced for effective tissue perfusion. O2 supplied to cells in 3D scaffoldsin vitrois initially dependent upon diffusion through the scaffold and cell consumption. Low O2 (3%) enhances specific cell behaviours, but where O2 is critically low (pathological hypoxia) cell survival becomes compromised. We measured real-time O2 in 3D scaffolds and introduced micro-channelled architecture to controllably increase delivery of O2 to cells and switch off the hypoxic response. Simple static micro-channelling gives adequate perfusion and can be used to control cell generated hypoxia-induced signalling.