Bottom-up biofabrication using microfluidic techniques

Nature builds living organisms in a bottom-up fashion, starting from the expression of genetic information on a cellular level, to the proliferation, differentiation, and self-assembly of cells into tissues/organs during embryo development and wound-healing processes. To mimic this bottom-up approach, it is essential to handle and manipulate small-scale biomaterials using specific technologies, such as microfluidic techniques. Microfluidics provides the tool-sets that deal with the behavior, precise control and manipulation of small amounts of fluids. Since the handling performed in aqueous environment guarantees the well-preserved bioactivities of biomaterials, microfluidic techniques show unique and critical advantages for biofabrication purposes. In this review, we report the recent progress on the bottom-up biofabrication using microfluidic techniques, such as the fabrication of microtissues, bioprinting of cell-laden tissue scaffolds, and organ-on-a-chip. As future perspectives, the deeper convergence of bottom-up approaches with top-down approaches as well as microfluidic-enabled vascularization of thick tissues is anticipated to have enormous impacts on the field of biofabrication.