Page 388 - IJB-9-3

International Journal of Bioprinting Bioprinting of a multicellular model

labor-intensive, and not universal. Two-dimensional (2D) screening model. The TME is composed of tumor cells,
cultures are an important model for drug screening and interstitial cells, extracellular interstitium, and cytokines
have been widely used. The 2D culture model is simple, secreted by each cell. TME plays an important role in
reproducible, and mature. The planar 2D structure is quite tumor proliferation, invasion, and metastasis [11,12] . Tumor
different from the three-dimensional (3D) spatial structure cells can influence proliferation through autocrine and
of the human body or animals. The influence of spatial paracrine mechanisms. Interstitial cells, such as immune
structure on cells, the interaction between cells, and the and endothelial cells, can also regulate the proliferation and
interaction between stromal cells and tumor cells has a invasion of tumor cells through immune mediators and
great influence on the morphological characteristics and secreted factors .
[13]
biological functions of tumor cells. In practice, antitumor 3D bioprinting is a convenient, efficient, economical,
drugs with significant inhibitory effects in 2D culture and easily standardized technology [14-16] . It can use tumor
models do not have good pharmacological effects after cells as “cell seeds” and accurately print according to the
application in the human body . model designed by researchers to construct a complex of
[4]
A 3D culture model was developed to improve the cells and bio-ink. In our previous work, 3D bioprinting
success rate of preclinical drug screening experiments technology was used to construct a human liver model
and to reduce research and development costs. The 3D that had good liver function in vitro and could maintain
culture model overcomes the limitations of 2D culture the functional state for a long time. The 3D bioprinted
plane structures in space to some extent. At present, tissue was used for transplantation therapy, which
different types of 3D culture models have advantages prolonged the survival of mice with liver failure .
[17]
and limitations [5,6] . For example, “sandwich” 3D culture This demonstrates the potential of using 3D bioprinted
still grows on a flat surface, tumor cells are stacked layer human liver tissue as a substitute for tissue from donor.
by layer, no real spatial structure has been established For drug screening, we constructed a 3D bioprinted
between cells, and cells still lack 3D interaction. Organoid hepatocellular carcinoma (HCC) cell model. The 3D
[18]
culture is an important research model in the field of stem bioprinting technology has good applicability in drug
cell research. Cells can be cultured with stem cell activity screening model construction. The results suggested that
through induction, reverse differentiation, and other steps the 3D bioprinted single-cell HCC model had unique
to form tissues with certain organ functions. At present, gene expression profiles and confirmed the advantages
the organoid model is limited by a number of factors, of the 3D bioprinted model over the traditional planar
such as low modeling success rate, complex process, culture model in terms of liver function and tumor-related
consumption of various expensive growth factors, and biological activities. We also validated primary HCC
high cost in the culture process. Patient-derived xenograft cells based on this model and predicted the treatment
(PDX) models have been widely used in colorectal response of patients with HCC to specific drugs using a
[7]
[19]
cancer research . In the PDX model, tumor tissues were 3D bioprinted model to guide personalized treatment .
inoculated subcutaneously into severely immunodeficient The establishment of a drug screening model for HCC
mice to allow for tumor growth in vivo. In this model, based on 3D bioprinting technology brings new directions
tumor tissues retain the characteristics of primary tumors and hope for the development of antitumor drugs .
[20]
to a large extent in terms of morphology, molecular Based on the successful experience of 3D bioprinted
biology, and other aspects. The PDX model showed good single-cell models, we explored the function of stromal
clinical predictability in preclinical drug screening studies. cells in cholangiocarcinoma by 3D bioprinting immune
However, there are also some problems with PDXs, such microenvironment model. At present, researchers have
as ethical disputes, more time consumption, high cost, used 3D bioprinting technology to explore tumor models
and complicated operation [8,9] . At present, suitable in vitro with various features and evaluate their application value
tumor models for drug screening are urgently needed in in drug screening and cancer research [21,22] . However,
clinical practice, and it is important to develop new drug current research on 3D bioprinting at home and abroad
screening models. focuses on the optimization of the printing process, the

As early as 2012, a study suggested that tumor selection of bio-ink, and the optimization of cell viability
[23]
microenvironment (TME) would have an impact on status , but there is still a lack of comprehensive and
tumor chemotherapeutic resistance . The development in-depth biological function evaluation and drug dose-
[10]
of new drug screening models should fully consider the response experiments of 3D bioprinted tumor models.
possible impact of the TME on colorectal cancer cells, To explore the potential value of the 3D bioprinted
which is helpful in building a real and effective drug model in colorectal cancer drug screening, we constructed

Volume 9 Issue 3 (2023) 380 https://doi.org/10.18063/ijb.694