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International

Journal of Bioprinting

RESEARCH ARTICLE
Fabrication of an in vitro three-dimensional

tumor model using liver-derived decellularized
extracellular matrix/gelatin methacrylate bioink

for investigating cancer characteristics and
drug resistance

Chunyang Zhang 1,2† id , Yunze Xu 1,2† , Hongwei Yu , Xiaochang Lu ,
1,3
1,2
Ying Fang , Changyong Li , Weihong Ji 1,3 id , Shibin Wang ,
1,3
1,2
1,2
Aizheng Chen 1,3 id , and Chaoping Fu *
1,2 id
1 Institute of Biomaterials and Tissue Engineering & Fujian Provincial Key Laboratory of Biochemical
Technology, Huaqiao University, Xiamen, Fujian, China
2 College of Materials Science and Engineering, Huaqiao University, Xiamen, Fujian, China
3 College of Chemical Engineering, Huaqiao University, Xiamen, Fujian, China
(This article belongs to the Special Issue: Advanced Strategies in 3D Bioprinting for Disease Modelling)

Abstract
† These authors contributed equally
to this work. Three-dimensional (3D) printing has emerged as a promising technique for creating
*Corresponding author: in vitro tumor models that replicate the tumor microenvironment, with the potential
Chaoping Fu to reduce or replace the use of experimental animals. The incorporation of 3D
(fuchp@hqu.edu.cn) decellularized extracellular matrix (dECM) hydrogels significantly enhances cellular
Citation: Zhang C, Xu Y, Yu H, responsiveness and functionality in drug screening. However, the limited printability
et al. Fabrication of an in vitro of dECM restricts its application in ex vivo 3D disease models. To address this
three-dimensional tumor model
using liver-derived decellularized limitation, researchers have developed a blended bioink composed of dECM, gelatin
extracellular matrix/gelatin methacrylate (GelMA), and gelatin, specifically tailored for direct ink writing-based 3D
methacrylate bioink for bioprinting. This formulation exhibits favorable shear-thinning behavior, enhanced
investigating cancer characteristics
and drug resistance. viscosity, and thermal-sensitive properties, making it suitable for 3D bioprinting. The
Int J Bioprint. 2025;11(4):392-408. combination of dECM with GelMA and gelatin not only improves the printability of
doi: 10.36922/IJB025160142 the bioink but also enhances the resolution of the printed scaffolds. Furthermore,
Received: April 14, 2025 dECM demonstrated positive effects on human hepatocellular carcinoma (HepG2)
Revised: May 24, 2025 cells, promoting proliferation, migration, and cell spheroid formation. A 3D liver
Accepted: June 9, 2025 cancer model was successfully created in vitro by printing HepG2 cells encapsulated
Published online: June 10, 2025
in the bioink containing dECM. This model exhibited characteristics akin to in vivo
Copyright: © 2025 Author(s). solid tumors, including notable cell proliferation, protein secretion, and substantial
This is an Open Access article
distributed under the terms of the cell spheroid formation (up to 78.83 ± 9.41 μm on day 8). Additionally, it showed
Creative Commons Attribution drug resistance, with 46.23% and 31.34% cell viability observed at 100 μg/mL
License, permitting distribution, concentrations of doxorubicin and paclitaxel, respectively. These findings underscore
and reproduction in any medium,
provided the original work is the potential of bioprinted 3D tumor models composed of GelMA, gelatin, and dECM
properly cited. as valuable platforms for the evaluation of anticancer drugs.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in Keywords: 3D tumor model; Decellularized extracellular matrix; Drug evaluation;
published maps and institutional Gelatin methacrylate; Printability
affiliations.

Volume 11 Issue 4 (2025) 392 doi: 10.36922/IJB025160142