Multidirectional interstitial flow promotes microvascular network formation: insights from a square chip-based platform

Microvascular network formation is governed by a variety of factors, with interstitial flow (IF) playing a pivotal role. However, the impact of multidirectional IF (MDIF) on microvascular network development remains insufficiently explored. In this study, we developed a platform consisting of a Square chip capable of generating MDIF and a deep learning-based Vasculature-on-a-Chip Analysis Tool (VoCAT) for high-efficient analysis of vascular morphology on the chip. Using this platform, we demonstrated that microvascular networks formed on the Square chip exhibited intricate structural features with enhanced functionality. We also demonstrated its utility in modeling a tumor microenvironment with complex microvascular networks and observed enhanced tumor cell migration. This study provides the first evidence that MDIF promotes microvascular network formation, offering new perspectives for advanced in vitro vascular and disease research.