Configurable 2D and 3D spheroid tissue cultures on bioengineered surfaces with acquisition of epithelial–mesenchymal transition characteristics

Both two-dimensional (2D) and three-dimensional (3D) biomaterial-based culture platforms that are capable of mimicking the in vivo microenvironment to recapitulate the physiological conditions are vital tools in a wide range of cellular and clinical research. Here we report tissue cultures in a microfluidic chip that allows deterministic patterning of cells in 2D/3D. The chip contains a cell-supporting membrane bioengineered to attain either 2D or 3D cell patterns by selectable deposition of extracellular matrix molecules. Results show a cell-trapping rate as high as 97% in our microchip. Tuning of the surface enables not only highly controlled geometry of the monolayer (2D) cell mass but also 3D culture of uniformly sized multicellular spheroids. The 3D spheroid culture of human epithelial ovarian cancer cells in the microfluidic chip resulted in acquisition of mesenchymal traits—increased expressions of N-cadherin, vimentin and fibronectin—and lowered expression of epithelial marker (CD326/epithelial cell adhesion molecule) compared with that in traditional 2D cultures, which is indicative of epithelial–mesenchymal transition in the spheres. In conclusion, these results offer new opportunities to achieve active control of 2D cellular patterns and 3D multicellular spheroids on demand, and may be amenable toward the study of the metastatic processes by in vitro modeling.