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International Journal of Bioprinting Review of 3D bioprinted organoids
function. Glycol chitosan improves mechanical strength photocuring properties. Other components of the bioinks
and biocompatibility . Using hASCs/KEGC as bioinks, serve different functions; for instance, the photoinitiator
[40]
they were bioprinted by extrusion bioprinting technology, lithium phenyl (2,4,6-trimethylbenzoyl) phosphinate
and the printed cells remained highly viable and could (LAP) triggers chemical crosslinking between polymers,
be continuously cultured. In addition, nanoparticles are and HA improves biocompatibility and viscosity . By
[47]
widely used in bioinks because of their excellent properties. printing the dECM-HA bioink of mixed mouse crypts
It can interact with polymers to adjust their properties and GelMA/LAP pregel, and seeded with submucosal
and can also be used to transmit cellular signals. Alcala- cells, they successfully established a co-culture system of
Orozco et al. developed Sr-GelMA nanocomposite bioink submucosal cells and intestinal organoids and found that
consisting of strontium carbonate (Sr) nanoparticles and it enhanced the function and proliferation of ISCs. Zhang
GelMA, where GelMA provides good biocompatibility, et al. combined dECM with silk fibroin protein to develop
and Sr improves printability . They bioprinted hMSC/ SF-dECM bioink, in which dECM was derived from
[41]
Sr-GelMA with extrusion bioprinting technology, and the natural cartilage tissue and provided a matching ECM
printed cells maintained high viability (>95%). In addition, environment for bone marrow mesenchymal stem cells
Sr also promoted osteogenic differentiation of hMSCs. In (BMSCs). Silk fibroin improves mechanical strength .
[48]
addition, studies have shown that introducing solid micro The structure printed by this bioink mixed with BMSCs
scaffolds into composite bioinks can also improve the cell can support the proliferation of BMSCs and promote
viability of organoid bioprinting . cartilage differentiation (Figure 2).
[42]
Self-assembling peptides are highly similar to the 2.2. 3D bioprinting technology for organoid
ECM, both structurally and mechanically, and have bioprinting
been applied in bioprinting as a novel bioink material .
[43]
Cofiño et al. developed a bioink blend of self-assembling With the integration of organoids and 3D bioprinting
peptide RAD16-I with methylcellulose (MC). RAD16-I technology, more and more printing methods have been
is not immunogenic and cytotoxic, and can support the applied to the bioprinting of stem cells or organoids.
attachment, growth, maintenance, and differentiation of According to different principles, the commonly used
various cells. MC is added to enhance the viscosity of the printing methods are divided into three categories:
bioink . They used hMSCs/RAD16-I/MC as bioinks, extrusion-based bioprinting, droplet-based bioprinting,
[43]
[49]
and the printed structure has high shape fidelity and and photocuring-based bioprinting . In addition,
stability while maintaining high cell viability. Alhattab more new bioprinting technologies have been gradually
[50]
et al. developed two kinds of ultrashort peptide bioinks developed, such as coaxial bioprinting , acoustic
[52]
[51]
using Ac-Ile-Ile-Cha-Lys-NH2 (IIZK) and Ac-Ile-Cha- bioprinting , and magnetic bioprinting (Table 2,
Cha-Lys-NH2 (IZZK) peptide sequences, respectively, Figure 3).
and combined with human bone marrow mesenchymal 2.2.1. Extrusion‑based bioprinting
stem cells (hBM-MSCs) for bioprinting. The cells showed The extrusion-based bioprinting (EBB) technology
high activity after printing, and the two ultrashort peptide consists of two main parts: a fluid distribution system for
bioinks promoted the chondrogenic differentiation of extruding and an automatic robotic system for printing.
hBM-MSCs . The fluid distribution system is driven by pressure-assisted
[44]
dECM refers to the remaining ECM after the removal pneumatic, piston, or screw systems, and the bioink is
of cellular components from tissues through decellularized extruded from the nozzle and deposited in the form of
technology . Although dECM bioinks have limitations cylindrical silk . EBB technology can be used to print
[45]
[53]
such as low viscosity, poor mechanical properties, and biomaterials with viscosity ranging from 30 to 6 × 10 mPa/s,
7
fast degradation rate, they also have many outstanding suitable for bioinks with high viscosity. Its characteristics
advantages compared with natural and synthetic bioinks. of continuous deposition of filaments can provide better
DECM has excellent tissue-specific functions, provides structural integrity for bioprinting, so EBB technology has
cells with a natural ECM environment, and is rich in cell been widely applied in organoid bioprinting. However,
growth and differentiation factors and various proteins. EBB technology also has many limitations. Firstly, EBB
Due to these properties, dECM bioinks are gradually being technology’s resolution can only reach about 100 µm,
widely used in bioprinting . The limitations of dECM can which reduces printing accuracy and limits the function
[46]
be improved by mixing dECM with other bioink materials. of printing tissue. Secondly, high shear stress caused by
Xu et al. developed a novel bioink in which porcine extrusion of high-viscosity bioink reduces cell vitality, and
intestinal dECM provided an ECM environment, and the survival rate of cells after EBB technology printing is
photosensitive GelMA provided rapid gelation and good usually between 40% and 86%. It is significantly lower than
Volume 9 Issue 6 (2023) 79 https://doi.org/10.36922/ijb.0112

