The increasing interest in biotechnology has stimulated the researchers to scrutinize biological elements and learn from nature. However, little is known about the potential risks of the materials, especially with nanoscale, and the control of adverse effects is a high political priority in the world. Stem cells have great potential for use in biological and medical applications because of their remarkable ability to differentiate into all cell types of an adult, including osteoblasts. Many 3D models currently in practice, however, require expensive equipment, extensive expertise, and the most disadvantages of them is that they are far from the nature of human tissues. Prior to implant these cells in vivo, our research group have developed advanced threedimensional culture system (3D) using micro- and nano-scaled technology to obtain the fundamental knowledge of in vitro culture systems to enhance the proliferation and differentiation of mesenchymal stem cells (MSCs) towards tissue regeneration. We have developed a combinational technology of micro- and nano-scale materials for the fabrication of biodegradable composites together with an advanced 3D culture system to be a promising way to promote the culture of stem cells to be used in regenerative medicine therapies. The present study overviews our several experimental data of stem cells on the basis of biomaterials and tissue engineering technology.