Micropatterning of cell aggregate in three dimension for in vivo mimicking cell culture

Surface engineering techniques for cellular micropatterning are emerging as important tools to clarify the effects of the microenvironment on cellular behaviour, as cells usually integrate and respond to the microscale environment, such as chemical and mechanical properties of the surrounding fluid and extracellular matrix, soluble protein factors, small signal molecules, and contacts with neighbouring cells. Furthermore, recent progress in cellular micropatterning has contributed to the development of cell-based biosensors for the functional characterization and detection of drugs, pathogens, toxicants, and odorants. In this regard, the ability to control shape and spread of attached cells and cell-cell contacts through the form and dimension of cell-adhesive patches with high precision is important. Commitment of stem cells to different specific lineages depends strongly on cell shape, implying that controlled microenvironments through engineered surfaces may not only be a valuable approach towards fundamental cell-biological studies, but also be of great importance for the design of cell culture substrates for tissue engineering. In particular, surface engineering techniques for cellular micropatterning as spheroids are focused on in this review. To develop this kind of cellular microarray composed of a cell-resistant surface and cell attachment region, micropatterning a protein-repellent surface is important because cellular adhesion and proliferation are regulated by protein adsorption. The focus of this review is on the surface engineering aspects of biologically motivated micropatterning of two-dimensional surfaces with the aim to provide an introductory overview described in the literature. In particular, the importance of nonfouling surface chemistries is discussed.