In bone external mechanical load is mediated by interstitial fluid flow, which represents the messenger between the bone cells and the biomechanical cues that are induced by our physical activity. These cues contribute to the biomechanical bone adaption response. In vitro studies often use 2D flat substrates that provide important information on bone cell response to biomechanical stimuli. However, this approach may be limited, compared to the in vivo situation because the 3D organization of bone cell morphology, the matrix attachment and the pericellular fluid flow environment in vivo differ significantly from 2D monolayer cultures. By using chip-based 3D cultures of bone cells in microfluidic bioreactors and compressive force devices, we will focus on how bone cell functions are modulated by their biomechanical microenvironment in the context of bone regeneration.