3D bioprinted breast tumor-stroma models for pre-clinical drug testing
Patricia González‐Callejo, Paula Vázquez‐Aristizabal, Clara García‐Astrain, Dorleta Jiménez de Aberasturi, Malou Henriksen‐Lacey, Ander Izeta, Luis M. Liz‐Marzán
Abstract
The use of three-dimensional (3D) bioprinting has been proposed for the reproducible production of 3D disease models that can be used for high-throughput drug testing and personalized medicine. However, most such models insufficiently reproduce the features and environment of real tumors. We report the development of bioprinted in vitro 3D tumor models for breast cancer, which physically and biochemically mimic important aspects of the native tumor microenvironment, designed to study therapeutic efficacy. By combining a mix of breast decellularized extracellular matrix and methacrylated hyaluronic acid with tumor-derived cells and non-cancerous stromal cells of biological relevance to breast cancer, we show that biological signaling pathways involved in tumor progression can be replicated in a carefully designed tumor-stroma environment. Finally, we demonstrate proof-of-concept application of these models as a reproducible platform for investigating therapeutic responses to commonly used chemotherapeutic agents.