Most of the knowledge on cellular response to different cues, especially to physical signals, is largely based on studies conducted using 2 dimensional (2D) platforms. However, 2D evaluations are not able to recapitulate the conditions that cells encounter in vivo. Therefore, to recapitulate the native cell niche, 3D cell culture has gained growing attention in recent years. Yet, the cell culture scaffolds mimicking the hierarchical structure of native tissues are rare, and usually, homogeneous hydrogel matrices are employed. In our research we are employing biofabrication approaches to produce highly specific scaffolds, with precisely controlled physical and biochemical features – signals for cells. Thanks to the use of the printing technique, we will be able to decouple different physical, chemical, and biological cues, and explore their influence on cell performance. We are studying different bio-instructive features and identifying key cues for a specific cellular response, in order to develop new advanced material systems for cell culture and tissue engineering.