3D Cell Migration Chip (3DCM‐Chip): A New Tool toward the Modeling of 3D Cellular Complex Systems

Abstract 3D hydrogel‐based cell cultures provide models for studying cell behavior and can efficiently replicate the physiologic environment. Hydrogels can be tailored to mimic mechanical and biochemical properties of specific tissues and allow to produce gel‐in‐gel models. In this system, microspheres encapsulating cells are embedded in an outer hydrogel matrix, where cells are able to migrate. To enhance the efficiency of such studies, a lab‐on‐a‐chip named 3D cell migration‐chip (3DCM‐chip) is designed, which offers substantial advantages over traditional methods. 3DCM‐chip facilitates the analysis of biochemical and physical stimuli effects on cell migration/invasion in different cell types, including stem, normal, and tumor cells. 3DCM‐chip provides a smart platform for developing more complex cell co‐cultures systems. Herein the impact of human fibroblasts on MDA‐MB 231 breast cancer cells’ invasiveness is investigated. Moreover, how the presence of different cellular lines, including mesenchymal stem cells, normal human dermal fibroblasts, and human umbilical vein endothelial cells, affects the invasive behavior of cancer cells is investigated using 3DCM‐chip. Therefore, predictive tumoroid models with a more complex network of interactions between cells and microenvironment are here produced. 3DCM‐chip moves closer to the creation of in vitro systems that can potentially replicate key aspects of the physiological tumor microenvironment.