Nature does nothing uselessly (Aristotle: I.1253a8).This is also true for our human body,although it is highly complex made up of highly synchronized sub-systems and of a huge number of individual cells.When a body tissue or cells are placed in dish,flask or multi-wells,they undergo substantially changes because of the change of the cellular microenvironments,e.g.the immediate environment of each individual cell.To mimic the natural cellular microenvironment,we have to work on different fabrication methods and different materials in order to create favorable conditions,including patterned extracellular matrix and controlled flow dynamics with high spatial and temporal resolution.In both cases,a large number of investigations have been performed but there is still no a clear strategy for long term development.We noticed that the most of previous studies were focused on bio-compatible materials such as synthetic polymers,metals and ceramics which are relative easy to process and validated by implants.However,these materials should not be ideal for the control of cell-material interaction.We therefore propose to structure natural polymers such as collagen and gelatin for the creation of new types of scaffolds.Two examples of techniques,i.e.gel-embossing and electrospinning will be given to demonstrate the feasibility of such an approach.We also noticed that the commonly used culture platforms are based on either static (culture dish) or perfusion-based (embedded microfluidic channels) flow exchange which should not be optimal neither in term of biomimetic approach.We therefore propose a diffusion-based culture using open access microchannel networks.This approach allowed mimicking blood vessels and capillaries under pulsating conditions.Finally,we will discuss the implication of synthetic cellular microenvironment in other related fields such as cell migration monitoring,cancer cell trapping,etc.