Organoid bioprinting for vascularized tumor assembloids

Abstract

The complexity and heterogeneity of the tumor microenvironment significantly influence cancer progression and therapeutic outcomes, highlighting the need for physiologically relevant in vitro models. In this study, we present vascularized tumor assembloids (VTASs) constructed via organoid bioprinting using a cell aggregate-rich living gel composed of endothelialized hepatic tumor aggregates and suspended endothelial cells. These VTASs recapitulate dense, volumetric, and hierarchical tissue architectures with functional vasculature and hepatic characteristics. Drug screening revealed reduced apoptosis and delayed intracellular drug accumulation in VTASs with dense microvasculature compared with cell-based or sparsely vascularized models, demonstrating differential responses to cisplatin, sorafenib, combination therapy, and doxorubicin. Co-culture with immune cells captured monocyte–endothelial interactions under inflammatory stimulation. Upon in vivo implantation, VTASs formed perfused tumorlike structures that recapitulated key histological and functional features of human cancer. Thus, VTASs provide a scalable and physiologically relevant platform for studying tumor biology, immune interactions, and high-throughput anticancer drug evaluation.