Spotlight on Three Rs Progress.

Multimodal therapies which combine a range of treatments (i.e. surgery, chemotherapy and radiotherapy) are becoming the standard of care for some cancers, leading to the need for increasingly complex and clinically relevant in vitro models. A recent paper by Johnson et al. describes the development of a high-throughput bioprinted colorectal cancer (CRC) spheroid platform with high levels of automation, information content and low cell number requirement. To achieve this, the team developed a biocompatible ink of gelatin–alginate, which was seeded with a wide range of CRC cell lines, bioprinted into a 96-well plate format, and cultured to induce spheroid formation. The cells in the bioink spontaneously aggregated into tightly organised spheroids, displaying tight cell–cell junctions, bioink matrix–cell interactions and hypoxic cores. As the cell requirements are lower compared to other systems, this platform is particularly suitable when cell availability is low (e.g. when patient-derived biopsies are used). To evaluate drug sensitivity, the spheroids were treated with two chemotherapy drugs, oxaliplatin (OX) and fluorouracil (5FU), and shown to be more resistant to the drugs than the respective cell monolayers. Furthermore, the applicability of this platform to treatment strategies including radiotherapy was confirmed by exposing the bioprinted spheroids to γ irradiation and successfully assessing radiation-induced cytotoxicity. Importantly, the effects of both chemotherapy and radiotherapy can be quantifiable with the same automated imaging approach, which highlights the potential of this platform for personalised medicine.