AccScience Publishing / IJB / Volume 12 / Issue 3 / DOI: 10.36922/IJB026200188
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RESEARCH ARTICLE

3D bioprinting of patient-derived cholangiocarcinoma organoids in a decellularized liver matrix-based bioink for drug testing

Qiumei Yan1† ,  Wenqi Hu2,3† ,  Jiashu Wang2,3 ,  Luping Lü2,3 ,  Zhuge Yang2,3 ,  Zixuan Pan2,3 ,  Yonggang Guo2,3 ,  Jie Liu2,3 ,  Huanhuan Chen2,3 ,  Di Wu2,3,4 ,  Qijun Du2,3,5 ,  Haijie Hu6 ,  Bin Lai2,3 ,  Yabao Liu2,3 ,  Guohua Wu7,8* ,  Xiongwen Chen1* ,  Bangchuan Hu9*
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1 Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, Department of Biopharmaceuticals, School of Pharmacy, Tianjin Medical University, Tianjin, China
2 College of Biomedical Engineering, Sichuan University, Chengdu, Sichuan, China
3 National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, Sichuan, China
4 Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
5 State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, Sichuan, China
6 Division of Biliary Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China
7 Luoyang Key Laboratory of Clinical Multiomics and Translational Medicine, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan, China
8 Henan Key Laboratory of Rare Diseases, Endocrinology and Metabolism Center, The First Affiliated Hospital and College of Clinical Medicine, Henan University of Science and Technology, Luoyang, Henan, China
9 Emergency and Critical Care Center, ICU, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China
†These authors contributed equally to this work.
IJB 2026, 12(3), 026200188 https://doi.org/10.36922/IJB026200188
Received: 13 May 2026 | Revised: 11 June 2026 | Accepted: 15 June 2026 | Published online: 15 June 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Cholangiocarcinoma (CCA) shows marked interpatient heterogeneity in chemotherapy response, highlighting the need for physiologically relevant, standardized, and reproducible in vitro models for individualized drug screening. However, Matrigel-based organoid models lack hepatobiliary extracellular matrix cues, and many bioprinting strategies rely on dissociated or fragmented organoids, disrupting native architecture and spatial organization. To address these limitations, we developed a composite bioink for direct bioprinting of patient-derived CCA organoid (CCAO) fragments that retained multicellular organization, enabling standardized culture, imaging, and drug-response evaluation. Although decellularized liver matrix (DLM) was used to reconstruct the tissue-specific microenvironment, its weak gelation, poor mechanical properties, and limited printability restricted its application. Tris(2,2’-bipyridyl)ruthenium(II)/sodium persulfate (Ru/SPS) and gelatin methacryloyl (GelMA) were introduced to improve photocrosslinking, mechanical support, and printability. DLM retained key components of the hepatic extracellular matrix, including collagen, fibronectin, laminin, and glycosaminoglycans. With GelMA and Ru/SPS, the bioink achieved rapid visible-light crosslinking (405 nm, 50 seconds), tunable mechanical properties, and good extrusion-printing compatibility. Among the tested formulations, the DLM-Ru/SPS:GelMA (4:1) group showed the best balance of printability, transparency, and organoid-compatible microstructure. Using this optimized bioink, organoid fragments were patterned and reassembled into viable spheroids that retained key CCA features and maintained high viability (>80%). The platform also enabled reproducible assessment of drug response, demonstrating dose-dependent cisplatin sensitivity and enhanced cytotoxicity with cisplatin–gemcitabine treatment. In summary, this study established a DLM-based direct bioprinting platform for CCAOs and a standardized system for individualized therapeutic evaluation.

Graphical abstract
Keywords
Three-dimensional bioprinting
Bioink
Cholangiocarcinoma
Decellularized liver matrix
Patient-derived organoids
Drug screening
Funding
Foundation of China (grant no. 82272188), the National Key Research and Development Program of China (grant no. 2022YFA1105200), the Sichuan Central Guided Local Science and Technology Development Special Project (grant no. 2025ZYD0012), the Science and Technology Program of Sichuan Province (grant no. 2025JDRC0057), the “Jie Bang Gua Shuai” Science and Technology Project of Chengdu (grant no. 2024-JB00-00018-GX), and the Strategic Research Bureau of Chengdu Eastern New Area (grant no. 2024-DBXQ-KJYF002).
Conflict of interest
The authors declare they have no competing interests.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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