Within all biological tissues, the extracellular matrix (ECM) plays an essential role in providing a three-dimensional (3-D) microenvironment for the cellular elements. It provides the necessary cues to recapitulate developmental processes in cell differentiation and morphogenesis. It is urgently required to more faithfully approximate the nanostructure of ECM in the development of in vitro 3-D cell/tissue model for biological study, drug development and regenerative medicine. Micro- and nanoscale technologies have employed to mimic the microenvironment for better understanding and manipulation of cell behaviors and function. Here, two examples are shown as follow.

(i) Cell Behavior on Nanoscale Modifications of Polymer Surfaces

The interest in this issue derives from the need to optimize the surface of fibers, the diameters of which already are in the micron range prior to expansion of cell populations for cellular and tissue engineering applications. The surface topography upon which cells grow is one of the factors that influence cellular behavior. Polyethylene terephthalate (PET) disks are etched using oxygen plasma to produce uniform and decidedly nanoscale levels of surface roughness. The influence of nanoscale topography is examined in terms of its effects on morphology, cytoskeleton expression, proliferation, differentiation, and apoptosis. Three distinct cell types ƒ{ mesenchyme-derived, fibroblast-like cells, epithelial breast cancer cells, and placental trophoblast-like cancer cells are employed to determine whether surface topography on the nanometer scale could influence a broad range of cell types. The results indicate that nanoscale roughness contributes in only moderate ways to cellular adhesion, proliferation, and differentiation in the cell lines tested.

(ii) Stem Cell Development in Electrospun Nanofibrous Matrices

The highly porous 3-D association of ECM nanofibril is essential for the reproduction of physiological patterns of cell behavior. Electrospun polycaprolactone (PCL) nanofibrous matrix is used to mimic the ECM. Pluripotent embryonic stem (ES) cells, an unlimited cellular resource of multiple cell lineages, are seeded into electrospun nano-fibrous PCL scaffolds and differentiated into adipocytes, where fat cell morphogenesis are used as a test bed. It demonstrates that ES cells seeded into nano-fibrous scaffolds rapidly differentiate into adipocytes that exhibit many fat cell functions, including expression of adipogenic proteins, accumulation of neutral lipid, insulin signaling, and ƒ"-agonist responsiveness. Thus, a 3D culture system is established to mimic microstructure and function of 3D adipose tissues in the body. This approach provides unprecedented potential for in vitro study of stem cell biology, early drug screening/testing and cellular medicine.