3D Additive Manufacturing and Micro-Assembly for Transfection of 3D-Cultured Cells and Tissues

3D additive manufacturing, namely 3D printing, has been increasingly needed in the fabrication of biological materials and devices. Compared to traditional fabrication, direct 3D digital transformation simplifies the manufacturing process and enhances capability in geometric fabrication. In this paper, we demonstrated a rapid and low-cost 3D printing approach for “lego” assembly of micro-structured parts as an electro-transfection device. Electro-transfection is an essential equipment for engineering and regulating cell biological functions. Nevertheless, existing platforms are mainly employed to monolayer cell suspensions in vitro, which showed more failures for translating into tissues and in vivo systems constituted by 3D cells. The knowledge regarding the three-dimensional electric transport and distribution in a tissue microenvironment is lacking. In order to bridge the gap, we assembled PDMS parts molded from 3D-printed molds as the 3D-cell culture chamber, which connects arrays of perfusion channels and electrodes. Such design allows spatial and temporal control of electric field uniformly across a large volume of 3D cells (10⁵∼10⁶ cells). Most importantly, multi-dimensional electric frequency scanning creates local oscillation, which can enhance mass transport and electroporation for improving transfection efficiency. The COMSOL electrostatic simulation was employed for proof of concept of 3D electric field distribution and transport in this “lego” assembled electro-transfection device, which builds the foundation for engineering 3D-cultured cells and tissues.