3D in vitro cancer models are important therapeutic and biological discovery tools, yet formation of matrix-embedded multicellular spheroids prepared in high-throughput (HTP) and in a highly-controlled manner remains challenging. This is important to achieve robust and statistically relevant data. Here, we developed an enabling technology consisting of a bespoke drop-on-demand 3D bioprinter capable of HTP printing of 96-well plates of spheroids. 3D-multicellular spheroids are embedded inside a hydrogel matrix with precise control over size and cell number, with the intra-experiment variability of embedded spheroid diameter coefficient of variation (CV%) being between 4.2%-8.7%. Application of 3D bioprinting HTP drug screening was demonstrated with doxorubicin. Measurements of IC50 values showed sensitivity 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 as a robust high-throughput platform to screen biological and therapeutic parameters. This talk we start by discussing the development of the bioprinter and different generations synthetic hydrogel bioinks that serve as the extracellular matrix mimics. The inks are compatible with drop-on-demand printing and provide fine control over the stiffness of the hydrogels, their porosity and the expression of bioactive components such as cell adhesive or cell remodeling ligands. We the show the application of the technology to drug screening and cell migration assays before finishing on our plans for using the methods for understanding the liquid biopsy and personalized medicine.

A 3D bioprinter specifically designed for the high-throughput production of matrix-embedded multicellular spheroids

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.