Open-Volume Microfluidics for Bioprinting of In Vitro Tumor Models

Abstract

The microenvironment of cancer cells has been demonstrated to have a profound influence upon both, tumor progression, as well as on their response to drugs. Control over the microenvironment is an essential element in the generation of physiologically relevant in vitro models. This would enable natural cell-to-cell interaction between various cell types, which is an increasingly important aspect within cancer research. In order to influence microenvironments at the cellular level, we utilize an open-volume microfluidics for high-precision patterning of mammalian cells and generate confluent biological tissues. Within this technique, individual cells are circulated in a confined fluid volume close to a surface, to which they adhere. This surface can be a pre-coated substrate, employing extracellular matrix components, optimized for efficient cell attachment. Additionally, this surface can be a confluent layer of cells upon which cells can be patterned. To demonstrate our approach for in vitro tumor modelling, simple skin and liver cancer models were constructed using A431 and HaCaT cells, as well as Hep G2 and 3T3-J2 cells, respectively. The functionality of the liver cancer model was probed by measuring albumin production over three weeks, indicating the suitability of the model for prolonged studies. As a further demonstration, we co-printed neuroblastoma cancer cells (SH-SY5Y) and human mesenchymal stem cells (MSCs) for studying the interaction of cancer and stem cells. The presented microfluidic bioprinting technique has great potential for building physiologically relevant multicellular cancer models to advance the understanding of disease mechanisms and screening drug compounds.