Abstract: Provided are cell niche engineering platform which represents a valuable in vitro tool for investigating physiological and pathological cellular activities, an all-in-one technology to engineer cell niche (particularly soluble cell niche factors) with retained bioactivities, a mask-free, non-contact, biocompatible and multiphoton-based microfabrication and micropatterning method for engineering a spatially and quantitatively controllable soluble proteins/bioactive factors and cell-cell adhesion molecules. An universal cell niche engineering platform is provided that contributes to reconstituting heterogeneous native soluble cell niche for signal transduction modeling and drug screening studies.