The aim of this COST Action is to refine the present understanding of in vivo micro/macro-environment in order to reproduce in vitro the physiological system in the best possible way: surface topography, substrate stiffness, mechanical stimulation, chemical cues and localized density will be analyzed. This will allow to develop reliable “3D total guidance” in vitro models reducing the number of animals used and allowing a safe translation of the present basic knowledge in cell repair and regeneration from the laboratory bench to the clinical application, with a positive impact on every day’s life patients and general Health costs. Researches in this field are being performed by different groups in the EU, but efforts need to be coordinated in order to avoid duplication, set targets and guidance for future research and to standardize protocols through a large interdisciplinary collaborative EU network. These goals can only be achieved under a COST program.