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International Journal of Bioprinting Review of 3D bioprinted organoids

(CAFs), which could accurately simulate the pathological cells in the printed tissue to be close enough for cell-to-
characteristics of tumors in vivo. The study proved that cell communication. However, most current bioprinting
bioprinted tumor assemblies have the same drug response methods are unsuitable for high-cell density bioinks,
as manually constructed tumor assemblies, and at the same and resolution and printing speed are limited. Finally,
time can be used for high-throughput drug screening [105] . insufficient vascularization of organoids is also a problem
that needs to be addressed. Microfluidic technology and
5. Future outlook and summary four-dimensional (4D) bioprinting technology may be the
effective ways to solve the above problems.
Organoid growth factors are mainly produced from
patient-derived induced pluripotent stem cells and human The application of microfluidic technology to the real-
stem cell differentiation. Due to their excellent ability to time distribution of cell concentration can successfully
simulate human development and diseases, organoids assist bioprinting to realize the construction of tissues and
[111]
have great application potential in drug testing and future organoids with high cell density . Microfluidics can also
organ replacement. However, organoids cultivated by be applied to the vascularization of organoids by printing
[112]
traditional methods have size, complexity, and maturity microfiber scaffolds to construct vascularized tissues .
limitations. Its more comprehensive application has been Since the microenvironment of 3D bioprinting structure
severely limited [106] . Bioprinting is regarded as a promising may not elicit appropriate biological responses, which
biomanufacturing technology because it can accurately will limit the application of 3D bioprinting, recently,
deposit bioink materials and cells in space. 4D bioprinting technology has been investigated to
solve the abovementioned problems. 4D bioprinting is a
Bioprinting has been shown to improve the size technology that combines 3D bioprinting with stimulus-
limitations of traditional organoid culture techniques. response materials, also known as innovative materials,
Bioprinting-Assisted Tissue Emergence (BATE) technique which can change their properties according to stimuli.
prints stem cells or organoids into an ECM that encourages Therefore, the structure of 4D bioprinting can more
spontaneous self-organization using extrusion-based accurately simulate native tissues [113] . Photocured silk
bioprinting technology and microscopy. This enables the fibroin (Sil-MA) hydrogels can deform in a typical cell
construction of centimeter-scale intestinal organoids by culture medium, and the tracheal structures obtained
controlling geometry and cell density [107] . Bioprinting also by combining with DLP bioprinting technology have
enables repeatable, consistent construction of organoids. A great application potential in regenerative medicine [114] .
new immersion bioprinting technology prints organoids However, 4D bioprinting is still at an early stage of
in a support bath with HA as the suspension medium, development, and more research is needed in the future.
avoiding the influence of orifice wall on printing during More recently, a strategy to apply artificial intelligence
the manufacture of high-throughput organoids, and the (AI) to organoid bioprinting has also been proposed, with
printed organoids have a high degree of consistency in the potential to build more standardized organoids with
volume and geometry [108] . an improved resolution by leveraging AI’s monitoring and
However, there are still many shortcomings in verification capabilities [115] .
bioprinting organoids. Firstly, in terms of bioinks, Since single organoid bioprinting cannot fully predict
organoid bioprinting has high requirements for the crosstalk between organs, organoid bioprinting may
bioinks. An ideal bioink material should possess the develop into multi-tissue organoid bioprinting in the
characteristics of biocompatibility, mechanical and future with the development of bioinks and bioprinting
structural integrity, biodegradability, non-cytotoxicity, techniques.
and immunogenicity, as well as the ability to provide a
highly biomimetic environment for cells. Besides that, it In summary, this paper introduces bioprinted
should be commercially available [109] . These requirements organoids, reviews the progress of bioinks, bioprinting
have greatly limited the development of bioinks, so it is techniques, and tissue vascularization strategies, and
urgent to create new formulations of bioinks. Recently, demonstrates the application of bioprinted organoids in
a new glycerohydrogel bioink has been proposed that biomedicine. Although there are still many shortcomings
demonstrates outstanding bacteriostatic properties and in bioprinting organoid technology, it is believed that with
long-term shape fidelity of printed tissues, as well as the development of research, this technology will be more
cytoprotection ability during printing, cryopreservation, mature.
and transportation [110] . The new bioinks could have great Acknowledgments
applications in organoid bioprinting. Secondly, in terms of
bioprinting technology, high-cell-density bioinks allow the None.

Volume 9 Issue 6 (2023) 89 https://doi.org/10.36922/ijb.0112