In general, the body tissue is composed of cells and their local environment. The environment plays an essential role in the attachment, proliferation, migration or differentiation of cells and the subsequent their 3-dimensional organization, which are important biological functions of cells to be investigated for cell-based tissue regeneration. The cell behavior is influenced by the surface and bulk properties of substrates for cell culture, such as the surface hydrophobicity, charge or morphology and the material stiffness. The proliferation and differentiation of cells can be biologically changed by the surface hydrophobicity and charge of culture substrates. The stiffness of culture substrates also modifies the differentiation profiles of stem cells. The combination of culture substrates with bioactive molecules promotes the proliferation and differentiation of stem cells. Various 3-demensional substrates are designed to demonstrate the effect of the mechanical and biological properties on the proliferation and differentiation of cells. Artificial manipulation of cell functions has been experimentally tried. Genetic engineering with transfection technology of plasmid DNA and small interference RNA (siRNA) enabled cells to activate their biological functions and modify their differentiation direction. This paper overviews basic researches on the interaction between cells and cultures substrates with different physicochemical properties. Several cell researches with different culture substrates are introduced to emphasize significance of biomaterial technology in the basic research of stem cells.