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; Marie Shinohara; Yasuyuki Sakai; Wei Sun

doi:10.1016/j.tibtech.2026.04.009

Organoid bioprinting for vascularized tumor assembloids

Trends Biotechnol. 2026 May 7:S0167-7799(26)00144-7. doi: 10.1016/j.tibtech.2026.04.009. Online ahead of print.

Authors

Zhenzhen Zhou¹, Yuan Pang², Zhendong Liao¹, Chang Zhou¹, Meiling Fu¹, Changru Liu¹, Yuting Guo¹, Kamto Yang¹, Jianyu He¹, Botao Gao³, Marie Shinohara⁴, Yasuyuki Sakai⁵, Wei Sun⁶

Affiliations

¹ Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing Institute for Intelligent Healthcare, Key Laboratory for Advanced Materials Processing Technology, Ministry of Education, Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China.
² Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing Institute for Intelligent Healthcare, Key Laboratory for Advanced Materials Processing Technology, Ministry of Education, Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China. Electronic address: pangyuan31@tsinghua.edu.cn.
³ National Engineering Research Center for Healthcare Devices, Guangdong Key Lab of Medical Electronic Instruments and Materials, Institute of Biological and Medical Engineering, Guangdong Academy of Sciences, Guangzhou 510632, China.
⁴ Institute of Industrial Science, University of Tokyo, Tokyo 153-8505, Japan.
⁵ Department of Chemical System Engineering, Graduate School of Engineering, University of Tokyo, Tokyo 113-8656, Japan.
⁶ Biomanufacturing and Rapid Forming Technology Key Laboratory of Beijing Institute for Intelligent Healthcare, Key Laboratory for Advanced Materials Processing Technology, Ministry of Education, Biomanufacturing Center, Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China; Department of Mechanical Engineering, Drexel University, Philadelphia, PA 19104, USA.

PMID: 42103601
DOI: 10.1016/j.tibtech.2026.04.009

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.

Keywords: assembloid; cell aggregates; living gels; microvascular network; organoid bioprinting; tumor microenvironment.