The living system in vivo is a complex system consisting of hierarchical microenvironment with flexible architectures,with size scales spanning from the micronto millimeter range.Engineering and microfluidic technologies are providingunprecedented opportunities to create physiologically relevant microenvironment cuesand facilitate the advances in understanding and developing new strategies for targetedtherapy in various diseases and regenerative medicine.In this talk,I will present themulti-scale engineering approaches that can be explored for facile fabrication andassembly of biomimetic materials,bio-interface and building blocks that are connectedto physiological microenvironment in vivo.I will also present the work of our lab inpursuing the bioinspired construction of patho-physiogical microenvironment (such asbrain and heart) at tissue or organ levels.