Introducing CELLBLOKS: a novel organ-on-a-chip platform allowing a plug-and-play approach towards building organotypic models.

Unlabelled: Human organs are structurally and functionally complex systems. Their function is driven by the interactions between many specialised cell types, which is difficult to unravel on a standard Petri dish format. Conventional "Petri dish" approaches to culturing cells are static and self-limiting. However, current organ-on-a-chip technologies are difficult to use, have a limited throughput and lack compatibility with standard workflow conditions. We developed CELLBLOKS as a novel "plug-and-play" organ-on-a-chip platform that enables straightforward creation of multiple cell-type organ-specific microenvironments. Herein, we demonstrate its advantages by building a liver model representative of live tissue function. CELLBLOKS allows one to systematically test and identify various cell combinations that replicate optimal hepatic relevance. The combined interactions of fibroblasts, endothelial cells and hepatocytes were analysed using hepatic biochemistry (CYP3A4 and urea), cellular proliferation indices and transporter activities (albumin). The results demonstrate that optimal liver function can be achieved by exploiting crosstalk in co-culture combinations compared to conventional mono-culture. The optimised CELLBLOKS liver model was tested to analyse drug-induced liver toxicity using tamoxifen. The data suggests that our CELLBLOKS liver model is highly sensitive to toxic insult compared to mono-culture liver models. In summary, CELLBLOKS provides a novel cell culture technology for creating human-relevant organotypic models that are easy and straightforward to establish in laboratory settings.

Supplementary Information: The online version contains supplementary material available at 10.1007/s44164-022-00027-8.