Hierarchical Vessel Network-Supported Tumor Model-on-a-Chip Constructed by Induced Spontaneous Anastomosis

[Image: see text] The vascular system in living tissues is a highly organized system that consists of vessels with various diameters for nutrient delivery and waste transport. In recent years, many vessel construction methods have been developed for building vascularized on-chip tissue models. These methods usually focused on constructing vessels at a single scale. In this work, a method that can build a hierarchical and perfusable vessel networks was developed. By providing flow stimuli and proper HUVEC concentration, spontaneous anastomosis between endothelialized lumens and the self-assembled capillary network was induced; thus, a perfusable network containing vessels at different scales was achieved. With this simple method, an in vivo-like hierarchical vessel-supported tumor model was prepared and its application in anticancer drug testing was demonstrated. The tumor growth rate was predicted by combining computational fluid dynamics simulation and a tumor growth mathematical model to understand the vessel perfusability effect on tumor growth rate in the hierarchical vessel network. Compared to the tumor model without capillary vessels, the hierarchical vessel-supported tumor shows a significantly higher growth rate and drug delivery efficiency.