Page 118 - IJB-9-1

International Journal of Bioprinting Fabrication of 3D breast tumor model for drug screening

1. Introduction material can be destroyed by high pressure; therefore, the
bioink must have a high viscosity in order to maintain the
Cancer is a disease with extremely high morbidity and structure of extruded material intact .
[15]
mortality. According to a report of the World Health
Organization (WHO), the mortality rate of cancer has Extracellular matrix (ECM) is an important component
surpassed that of coronary heart disease and stroke, in biological tissues, which supports cell growth and is
and cancer is recognized for contributing to the involved in various complex cell–cell and cell–matrix
[1]
highest mortality worldwide . The latest survey by the interactions, as well as the release and reception of
International Agency for Research on Cancer (IARC) in biochemical signals. ECM is a highly dynamic structure
2020 showed that breast cancer is the most common cancer which is constantly reshaped by cells in tissues through
in women, and also one of the cancers with the highest synthesizing and degrading various chemical components
mortality worldwide. Therefore, research on breast cancer and reorganizing their 3D structure. These complex
has become extensive in the research community . Using processes require strict regulation to maintain tissue
[2]
in vitro tumor models constructed by tissue engineering homeostasis, and imbalance of ECM remodeling may lead
[16]
method to study the mechanism of cancer and perform to disease . In tumor tissues, the composition, content,
anti-cancer drug screening is very common. However, and structure of ECM are related to tumor type, degree of
the development of traditional two-dimensional (2D) malignancy, and stage of development. In clinical treatment,
tumor models is limited by the growth environment they ECM molecules can be used as indicators to predict tumor
[17]
confer that cannot accurately mimic the heterogeneity and prognosis . Studies have shown that remodeling of ECM
complexity of tumor tissues in vivo. In addition to tumor plays an important role in the formation and development
cells, multiple types of stromal cells, such as fibroblasts, of tumors, during which the composition and content of
endothelial cells, and immune cells, as well as complex ECM in tumor tissues may change. Therefore, the study of
network of blood vessels and extracellular matrix structure, in vitro ECM and its remodeling is conducive to further
[18]
exist within tumor microenvironment [3,4] . Therefore, three- investigation of the pathogenesis of tumors . Currently,
dimensional (3D) tumor models and their construction the materials commonly used to construct in vitro ECM
have been widely studied in recent years. 3D scaffolds as tissue engineering scaffold can be divided into natural
fabricated with various desired materials can simulate the materials and synthetic materials. Natural materials
[22]
[21]
[19]
[20]
complex extracellular matrix components and structures include gelatin , alginate , chitosan , collagen ,
[23]
of tumor microenvironment that be unattainable for 2D decellularized extracellular matrix (dECM) , and
[24]
counterparts, and they are often used as a bridge between hyaluronic acid (HA) , etc. Synthetic materials include
[25]
2D-level researches and animal experiments [4,5] . polylactic acid glycolic acid (PLGA) , polycaprolactone
(PCL) and polyethylene glycol (PEG) , etc. Natural
[26]
[27]
In the process of constructing 3D tumor models, it is very materials exhibit good biocompatibility and can provide
important to choose appropriate methods and materials effective support for cell growth but often have limited
to prepare scaffolds for cell growth. 3D bioprinting is an physical properties, while synthetic materials show good
effective additive manufacturing technology. Living cells, physical properties but lack the sites for cell attachment.
biochemical factors, proteins, drugs, and other biological
materials were deposited on solid or gel surfaces or liquid dECM is a natural material commonly used to construct
collectors through layer-by-layer stacking of bioink tissue engineering models. It is a biological macromolecular
to construct functional biomaterials [6–8] . By writing and network obtained after the removal of cell components in
controlling the computer program, this technology can biological tissues. It retains the structure, various chemical
achieve precise control of cell distribution and material components, and vascular network of ECM, which could
structure, thereby printing tissue engineering scaffold, promote cell proliferation and tumor progression .
[28]
which is flexible and adjustable for different models dECM had been reported to increase normal cell migration
and applications [9,10] . Due to its advantages in accurate and invasion of cancer cells, and regulate cell behavior to
reproducibility, high throughput, and high efficiency, maintain tissue integrity [23,29] . According to statistics, more
3D bioprinting has been gradually applied in tissue than 50% of the patients diagnosed with breast cancer
[30]
engineering in recent years . 3D bioprinting technologies develop liver metastasis . Owing to the association of the
[11]
include material extrusion , material jetting, and vat liver with metabolism of xenobiotics and drugs in the body,
[13]
[12]
polymerization , among which material extrusion is the liver proves to be a very challenging site for antimetastatic
[14]
the most widely used printing method on the grounds chemotherapies . Therefore, it is imperative to establish
[30]
of simplicity and low cost. Nevertheless, since extrusion a tumor model simulating liver microenvironment for
printing involves the squeezing of the bioink out of the continuous adhesion, proliferation, and invasion of breast
nozzle through a pressure system, the structure of the cancer cells for the screening of antimetastatic drugs of
Volume 9 Issue 1 (2023) 110 https://doi.org/10.18063/ijb.v9i1.630