A rapid high throughput bioprinted colorectal cancer spheroid platform for in vitro drug- and radiation-response

We describe the development of a high-throughput bioprinted colorectal cancer (CRC) spheroid platform with high levels of automation, information content, and low cell number requirement. This is achieved via the formulation of a hydrogel bioink with a compressive Young's modulus that is commensurate with that of colonic tissue (1-3 kPa), which supports exponential growth of spheroids from a wide range of CRC cell lines. The resulting spheroids display tight cell-cell junctions, bioink matrix-cell interactions and necrotic hypoxic cores. By combining high content light microscopy imaging and processing with rapid multiwell plate bioprinting, dose-response profiles are generated from CRC spheroids challenged with oxaliplatin (OX) and fluorouracil (5FU), as well as radiotherapy. Bioprinted CRC spheroids are shown to exhibit high levels of chemoresistance relative to cell monolayers, and OX was found to be significantly less effective against tumour spheroids than in monolayer culture, when compared to 5FU.

Automated summary

This study describes the development of a high-throughput bioprinted colorectal cancer (CRC) spheroid platform that is highly automated and provides rich information content, with low cell number requirement. By using a hydrogel bioink with a compressive Young's modulus similar to that of colonic tissue, spheroids from various CRC cell lines can grow exponentially. The study also found that bioprinted CRC spheroids exhibit higher levels of chemoresistance compared to cell monolayers.