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International Journal of Bioprinting Bioprinted liver dECM/GelMA tumor model

1. Introduction been used, they cannot fully replicate the complex ECM
in vivo, which is a crucial microenvironment for cells.
29
Cancer is a pervasive global public health challenge, The ECM is a complex and dynamic network that provides
significantly impacting human life and well-being. In essential structural support and significantly influences
recent years, effective treatments for cancer include various cellular functions, 30–33 including proliferation,
34
surgical resection, radiotherapy, and chemotherapy. migration, differentiation, 36,37 and signal transduction. 38,39
3,4
5,6
1,2
35
Nevertheless, the 5-year survival rate of patients remains Consequently, accurately simulating or reconstructing the
suboptimal. On one hand, current treatments fail to achieve ECM in vitro is critical for developing tumor models that
a complete cure. On the other hand, our understanding of closely mimic physiological conditions. 40,41
the complex mechanisms and characteristics of tumors
remains incomplete, hindering the development of effective Decellularization technology offers a promising
7,8
therapies and drugs. Currently, preclinical research on method to selectively eliminate cellular components
anticancer drugs heavily relies on two-dimensional (2D) from tissues or organs while retaining the essential ECM
cell and animal models. However, the simplicity of 2D cell components, biological functions, and structural integrity.
models and the limitations of animal experiments, such This advanced technique has significantly broadened the
as long timelines, limited reproducibility, and high costs, use of ECM materials in the biomedical field. 42,43 However,
hinder the development of effective tumor treatments. 9–11 decellularized ECM (dECM)-based bioinks suffer from
Thus, there is an urgent need for sophisticated models suboptimal printability due to inadequate mechanical
that accurately simulate three-dimensional (3D) solid properties, unstable thermo-responsive behavior, and
tumors in vivo. Such models hold great promise for variable rheological properties, which limit their broader
44,45
facilitating more comprehensive tumor research, application in 3D bioprinting.
improving pharmacological evaluations, and accelerating In this study, we aimed to tackle the challenges posed by
drug development. the limited printability of dECM-based bioinks while also
developing an optimized bioink derived from liver tissue
The emergence of 3D cell culture technology has
revolutionized the advancement of in vitro tumor that demonstrates superior 3D printability. Our formulation
not only improved printability but also exhibited excellent
models. Within a 3D culture system, the establishment biocompatibility and favorable interactions with HepG2
of an extracellular matrix (ECM) and the incorporation cells, a liver cancer cell line. To comprehensively evaluate
of diverse signals that mimic the growth characteristics the physical and biological attributes of our bioink,
of tumor cells are of utmost importance. 12–15 Through we conducted a series of assessments encompassing
the implementation of 3D culture, tumor models can be morphology analysis, rheological characterization,
meticulously crafted by manipulating the properties of the degradation evaluation, swelling behavior analysis, 3D
matrix or scaffold, thereby facilitating the investigation of printability testing, and cytotoxicity analysis.
morphogenesis, angiogenesis, invasion, pharmacology,
and other tumor-related attributes. 16,17 Consequently, 2. Materials and methods
3D bioprinting emerges as a promising approach for
the construction of standardized 3D tumor models. By 2.1. Materials
harnessing the capabilities of 3D printing technology, Gelatin, methacrylic anhydride, sodium dodecyl sulfate,
bioprinting enables the seamless integration of cells and ciprofloxacin were purchased from Aladdin Reagent
and biological materials, layer by layer, resulting in the Co., Ltd. (China). The porcine liver was procured from
generation of tissue-like structures. 18,19 Mankouxiang Ecological Farming Cooperative Co., Ltd.
(China). Cell Counting Kit (CCK)-8 and Dulbecco’s
Natural hydrogels like fibrinogen, cellulose, Modified Eagle Medium were obtained from Keygen
chitosan, alginate, and hyaluronic acid are extensively Biotech Corp., Ltd. (China). The bicinchoninic acid kit
used as bioinks in bioprinting for their controllable was purchased from Shanghai Biyuntian Biotechnology
mechanical properties and excellent biocompatibility. 20–23 Co., Ltd. (China). The DNA kit was obtained from Cwbio,
Bioprinting significantly enhances the reproducibility and China; the glycosaminoglycan (GAG) kit from Genmed,
standardization of 3D tumor models, making it ideal for China; and the collagen kit from Chondrex, United States of
preclinical research. 24,25 3D-bioprinted tissues help reduce America (USA). Paclitaxel (PTX) and doxorubicin (DOX)
model variability, improve the consistency and reliability were purchased from Solarbio Science and Technology
of drug screening data, and lower the risk and cost of drug Co., Ltd. (China). Calcein-acetoxymethyl/propidium
screening. 26–28 However, establishing a tumor model relies iodide and acridine orange/ethidium bromide reagent kits
on critical cellular, biochemical, and mechanobiological were obtained from Solarbio Science and Technology Co.,
cues. Although both natural and synthetic polymers have Ltd. (China).

Volume 11 Issue 4 (2025) 393 doi: 10.36922/IJB025160142