Logo image
Back
Organoid bioprinting for vascularized tumor assembloids
Journal article   Peer reviewed

Organoid bioprinting for vascularized tumor assembloids

Zhenzhen Zhou, Yuan Pang, Zhendong Liao, Chang Zhou, Meiling Fu, Changru Liu, Yuting Guo, Kamto Yang, Jianyu He, Botao Gao, …
Trends in biotechnology (Regular ed.)
07 May 2026
DOI: https://doi.org/10.1016/j.tibtech.2026.04.009
PMID: 42103601

Abstract

assembloid cell aggregates living gels microvascular network organoid bioprinting tumor microenvironment
Organoid bioprinting enables the fabrication of vascularized tumor assembloids that better replicate the architecture and cellular complexity of native tumors.Vascularized tumor assembloids overcome the limitations of conventional tumor spheroids by supporting high-density tumor growth with integrated microvascular networks.The platform enables spatiotemporal analysis of drug diffusion, penetration, and therapeutic response in vascularized tumor tissues.Vascularized tumor assembloids recapitulate key tumor microenvironment interactions, including tumor–vascular and immune–vascular crosstalk.Prevascularized organoid-rich living gel constructs rapidly integrate with host vasculature in vivo to form perfused tumorlike tissues. 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. The vascularized tumor assembloid platform currently corresponds to Technology Readiness Level 4, with performance validated under controlled laboratory conditions. Vascularized tumor assembloids recapitulate volumetric tumor architecture, microvascular networks, metabolic activity, and heterogeneous drug responses through a scalable organoid bioprinting workflow. The platform also enables the investigation of immune–tumor interactions in vitro and supports the formation of perfused, humanized xenografts in vivo. Key translational challenges include adaptation to good manufacturing practice standards, incorporation of patient-derived cells to capture interpatient variability, and integration of perfusion bioreactors for long-term culture and functional maturation. Continued progress will depend on standardized biomaterials, cell-sourcing strategies, and bioprinting protocols, as well as the development of regulatory frameworks that position vascularized tumor assembloids as advanced preclinical models, bridging in vitro systems and in vivo biology. This study introduces a bioprinted, vascularized tumor assembloid platform that recapitulates key features of the human tumor microenvironment, including functional microvasculature. This platform can analyze tumor–vascular and tumor–immune interactions, metabolism, and drug responses in dense 3D tissues, providing a scalable system for cancer modeling and therapeutic testing.

Metrics

1 Record Views

Details

Logo image