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tumor organoids printed with it retain features similar to Therefore, designing bioinks that incorporate inorganic
primary breast tumors, reconstructing key aspects of the biomaterials to generate functional 3D bioprinted
tumor microenvironment. Overall, optimizing bioinks organoids is highly valuable. For example, Zhang et al.
for 3D bioprinting significantly aids the construction and designed a bioink containing calcium silicate to print
development of organoids. a multicellular scaffold that mimics the distribution of
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Moreover, to better regulate cell behavior and promote bones and nerves. Calcium silicate significantly promotes
the development of multicellular 3D bioprinted scaffolds, osteogenic differentiation of stem cells and the neural
bioinks containing functional materials have proven to differentiation of Schwann cells. Inorganic biomaterials,
be a viable strategy. For example, research led by Prof such as calcium silicate-based bioinks, present an effective
Chunying Chen at the National Center for Nanoscience strategy for designing complex tissue constructs, such as
and Technology of China demonstrated that carbon bone organoids, through 3D bioprinting.
nanotubes could enhance the mechanical properties 5.2. Optimizing bioprinting parameters
of the extracellular matrix, activate the mechanical
sensing signaling pathway of cells, and regulate cellular In the process of using 3D bioprinting to develop
metabolism, including promoting mitochondrial organoids, the design of bioinks is not the only crucial
respiration and nutrient absorption, thereby facilitating the factor; the setting of the printing device also plays a
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development of intestinal organoids (Figure 6). Another significant role. The adjustment of printing parameters
bioink, incorporating iron oxide nanoparticles, enables the is directly linked to the structural characteristics of 3D
manipulation of organoid deposition and movement using bioprinting constructs. In addition, optimizing printing
a magnetized 3D printing device. This platform allows for device settings enhances the production and application
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the controlled and precise arrangement and combination of organoids.
of neural organoids derived from human induced To maintain an optimal 3D culture environment for
pluripotent stem cells and glioma organoids derived from liver cells derived from human induced pluripotent stem
patients (Figure 7). In addition, the inclusion of engineered cells, DLP-based 3D bioprinting has been used to develop
extracellular vesicles, known for their therapeutic efficacy microscale hexagonal constructs. This cultivation model
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in treating diseases, can also enhance the development of significantly promotes the phenotype and function of liver
functionalized bioinks. 72 cells, mimics the structure of liver modules, and provides
Inorganic bioactive materials possess excellent strategies for designing biomimetic 3D bioprinted livers.
biological functions, not only guiding the behavior of stem The key to this strategy is the use of hexagonal building
cells but also regulating the interactions between cells, blocks, which correspond to physiological scales similar
thereby positively affecting the development of stem cell- to lobular units. High-resolution 3D bioprinting allows
derived organoids. 73,74 For example, Ma et al. developed a the production of finer structural features, including
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composite hydrogel composed primarily of calcium silicate micropore size and curvature. Research has demonstrated
and methacrylate gelatin to support the development of that the micro-porous culture platform, designed by high-
organoids. Research has shown that bioactive ions released resolution 3D bioprinting, successfully generates mature
from calcium silicate promote the key signaling pathways human brain organoids. These organoids displayed key
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for organoid development, highlighting the potential structural features of the brain. In addition, by adjusting
application of inorganic biomaterials in organoid research. curvature and resolution, the development of organoids
Zhang et al. showed that MXene promotes the can be further optimized, highlighting the benefits of
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maturation of cochlear organoids, with regenerated modifying the 3D printing structure for developing
hair cells exhibiting electrophysiological characteristics improved organoid culture platforms. Moreover, regulating
similar to those of natural hair cells. They also printing pressure and needle settings during 3D bioprinting
demonstrated that MXene activates the mammalian aids in the standardized production of organoids. A study
target of rapamycin signaling to promote hair cell has shown that after incubation at 7°C for 30 min, printing
differentiation. Furthermore, in the co-culture system of paste can produce tumor organoids < smaller than 200 μm
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cochlear organoids and the modiolus, neural innervation on a standard glass substrate under a pressure of 7 – 15 kPa.
was established between regenerated hair cells and spiral Furthermore, a microchannel scaffold with a top channel
ganglion neurons, promoting synapse formation. These and four interconnected side channels has been designed
findings suggest that inorganic biomaterials, through by adjusting printing parameters. This scaffold facilitates
their influence on ion release, regulation of matrix the loading and embedding of organoids. Importantly,
mechanical properties, and promotion of organoid-cell the different channels provide conditions for inoculating
functional co-culture systems, are becoming increasingly various cell types, which is beneficial for studying the
integral to organoid research. interactions between cells and organoids. 81

Volume 1 Issue 1 (2025) 10 doi: 10.36922/OR025040004