MicroVasculoid-Chip: A 3D Self-Assembled Human Microcirculation-on-a-Chip Model Reveals Enhanced Lymphangiogenic Lung Cancer-Induced Vessel Remodeling and Invasion

The microvasculature within the tumor microenvironment is crucial for the invasion and dissemination of cancer cells throughout the body. Given its importance and dynamic behavior, several microfluidic models have been developed to study microvascular infiltration and its interaction with cancer cells. However, most of these models primarily focus on blood vessels and use microfluidic channels coated with endothelial cells, which fail to replicate near-physiological conditions. To address this limitation, the MicroVasculoid-chip is introduced, a novel human microcirculation-on-a-chip model that features self-organized 3D blood and lymphatic microvasculature alongside tumor spheroids. This innovative platform enables the exploration of interactions between multi-cellular tumors and both microvascular networks. Using lung cancer as a case study, how tumor-released mediators influence vessel morphology is investigated in relation to tumor invasion capacity, identifying molecular factors potentially associated with microvascular remodeling. Overall, the MicroVasculoid-chip provides a robust tool for investigating and modeling critical events of cancer neo-vascularization, for deciphering fundamental mechanisms of cancer cell invasion into the microvasculature, and for future drug screening applications.