A Programmable Multifunctional 3D Cancer Cell Invasion Micro Platform

Abstract In the research of cancer cell invasion and metastasis, recreation of physiologically relevant and faithful three‐dimensional (3D) tumor models that recapitulate spatial architecture, spatiotemporal control of cell communication and signaling pathways, and integration of extracellular cues remains an open challenge. Here, a programmable multifunctional 3D cancer cell invasion microbuckets‐hydrogel (Mb‐H) platform is developed by integrating various function‐variable microbuckets and extracellular matrix (ECM)‐like hydrogels. Based on this Mb‐H micro platform, the aggregation of multi‐cancer cells is well controlled to form cancer cell spheroids, and the guiding relationship of single‐cell migration and collective cell migration during the epithelial‐mesenchymal transition (EMT) of cancer cell invasion are demonstrated. By programming and precisely assembling multiple functions in one system, the Mb‐H platform with spatial‐temporal controlled release of cytokine transforming growth factor beta (TGF‐β) and various functionalized Mb‐H platforms with intelligent adjustment of cell‐matrix interactions are engineered to coordinate the 3D invasive migration of cancer cell spheroids. This programmable and adaptable 3D cancer cell invasion micro platform takes a new step toward mimicking the dynamically changing (localized) tumor microenvironment and exhibits wide potential applications in cancer research, bio‐fabrication, cell signaling, and drug screening.