A 3D Bioprinter Specifically Designed for the High-Throughput Production of Matrix-Embedded Multicellular Spheroids

3D in vitro cancer models are important therapeutic and biological discovery tools, yet formation of matrix-embedded multicellular spheroids in a throughput and highly controlled manner to achieve robust and statistically relevant data, remains challenging. Here, we developed an enabling technology consisting of a bespoke drop-on-demand 3D bioprinter capable of high-throughput printing of 96-well plates of spheroids. 3D-multicellular spheroids are embedded inside a tissue-like matrix with precise control over size and cell number. Application of 3D bioprinting for high-throughput drug screening was demonstrated with doxorubicin. Measurements showed that IC50 values were sensitive to spheroid size, embedding and how spheroids conform to the embedding, revealing parameters shaping biological responses in these models. Our study demonstrates the potential of 3D bioprinting in a tuneable and biologically relevant environment as a robust high-throughput platform to screen biological and therapeutic parameters.