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International Journal of Bioprinting Review of 3D bioprinted organoids

Organoids are widely used in disease modeling, drug as mechanical signaling pathways of extracellular matrix
development, and personalized treatment because their (ECM) materials. Bioprinting of organoids with complex
self-organizing characteristics are similar to biological structures remains a challenge .
[15]
intrinsic processes, enabling the simulation of the This paper reviews the recent progress and application
formation process and physiological and pathological state of bioprinting organoids. Firstly, the bioink and bioprinting
of organ tissues. Since 2020, significant research progress methods used in bioprinted organoids are introduced.
has been made in applying organoids to COVID-19 disease Secondly, the vascularization strategies of bioprinted
modeling [11,12] . To research how colon and alveolar cells organoids are summarized and analyzed in view of the
react to SARS-CoV-2 infection, Han et al. created human insufficient vascularization of traditional organoids. Then,
pluripotent stem cell (HPSC)-derived lung organoids the applications of bioprinted organoids in drug screening,
(hPSC-LOs) and colon organoids (hPSC-COs). By high- regenerative medicine, and tumor research are introduced.
throughput screening of pharmaceuticals that have received At the same time, the application of microfluidic
FDA approval, they also discovered three medications with technology and more advanced bioprinting methods
antiviral effectiveness against SARS-CoV-2 . to solve the defects of existing bioprinting organoids is
[12]
In order to give full play to the potential of organoid discussed. Finally, the article concludes with a summary
technology, the problems in organoid manufacturing must and a look into the possible future directions of developing
be solved. The culture method of organoids mainly relies bioprinting organoid technology (Figure 1).
on the traditional 3D culture technology, which utilizes
the self-organizing properties of stem cells. However, it 2. Organoid bioprinting
has many limitations, such as lack of repeatability, limited The selection of bioink and printing methods is critical
size, lack of vascular system, and communication between to realizing organoid bioprinting. Bioink is the necessary
immune cells and organs . Due to the above-mentioned condition for the success of organoid bioprinting. A
[13]
limitations, 3D bioprinting technology is currently applied suitable printing method can better play the characteristics
to organoid cultivation, replacing manual organoid of bioink and get a better printing effect. Here, we introduce
construction for growing more complex large organoids. currently used bioinks and printing methods.

3D bioprinting is derived from 3D printing (also known 2.1. Bioink for organoid bioprinting
as additive manufacturing [AM]). Unlike 3D printing, The printing materials used in 3D bioprinting are known
which uses adhesive materials such as powdered metal or as bioinks, and their properties are typically determined
plastic, 3D bioprinting uses bioinks as printing materials by three metrics: printability, biocompatibility, and
that are deposited layer by layer spatially to create a tissue- mechanical properties. Printability refers to the forming
like growth structure. The application of bioprinting characteristics of bioink, which is related to many
technology in organoid manufacturing can control the factors, such as the viscosity of the material and printing
composition and distribution of bioinks more accurately parameters. The bioink with good formability shows
compared with manual construction; hence, it is expected good flow during printing and can be cured quickly after
to realize the stable construction of organoids with high printing. Biocompatibility requires that the bioinks have
precision, high throughput, and batch automation. In 2021, an environment similar to the ECM in vivo, facilitating the
Lawlor et al. used extrusion bioprinting to successfully development and communication of cells after printing.
generate self-organizing kidney organoids with high Mechanical properties require the bioink to have sufficient
cell number and viability reproducibility. The produced strength to support the subsequent culture process . In
[16]
organs were comparable to manually engineered kidney addition, bioinks for stem cell and organoid bioprinting
organoids in terms of morphology, component cell types, need to be biodegradable and cell nontoxic. The selection
and gene expression levels, demonstrating the feasibility of of the most appropriate bioink in bioprinting is usually
replacing manual organoid engineering with bioprinting considered in combination with the specific target tissue,
methods. In addition, 3D bioprinting can also change the cell type, and bioprinting method .
[17]
biophysical characteristics of organoids, including volume
size, number of cells, and conformational configuration, The main components of bioink are cells and biological
which has excellent advantages . materials. Hydrogels are 3D network structure gels
[14]
composed of hydrophilic polymers through crosslinking,
At present, 3D bioprinting technology is mainly which can highly simulate a natural ECM environment
used for bioprinting stem cells for the construction of in vitro. They are the most widely used bioink materials.
organoids and then promoting the differentiation of stem Hydrogel bioinks usually comprise natural polymers,
cells through growth factors and small molecules, as well synthetic polymers, and decellularized extracellular

Volume 9 Issue 6 (2023) 76 https://doi.org/10.36922/ijb.0112