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International Journal of Bioprinting Multi-Cellular tissues/organoids manufacturing strategies

On the other hand, as shown in Figure 5C, the system integrates an extrusion-based printing system,
sacrificial bioprinting technique reverses the support bath a support bath printing system, and a manual control
paradigm. Here, a sacrificial ink is printed into a slurry- console system. This system provides an effective method
like support bath composed mainly of cellular spheroids . of spatial 3D positioning: the extrusion-based printing
[87]
By combining a suitable extracellular matrix and organ system creates precise spatial templates, the manual control
building blocks, the support bath exhibits shear-thinning system regulates the spatial position of the syringe pump’s
behavior, yielding ahead of the printing nozzle and self- tip, and the bioprinted bioink is extruded into a suspension
healing behind it, similar to traditional embedded printing bath and crosslinked at 37°C to maintain stability in the
techniques that use microgels. Notably, the extracellular spatial environment.
matrix solution alone lacks the necessary rheological The sphere-based modular assembly method has
properties to support embedded 3D printing. However, the limited applicability, and biofabrication technologies
extracellular matrix stiffens at physiological temperatures, based on cells or spheroids assembly must consider
preserving the geometry formed within the organ building size control, production efficiency, heterotypic cell co-
blocks by the sacrificial ink during its removal. culture, vascularization, as well as in vitro pretreatment
The sacrificial bioprinting technique enables the and maturation . This method is unsuitable for tissues
[51]
generation of networks of perfusable tubular features or organoids with high mechanical properties, such
within the printed constructs, which can serve as templates as muscles and bones, as these tissues or organoids
for vascular channels exceeding 40 mm in length and typically thrive under high physiological conditions .
[70]
4 mm in thickness. Cell viability is maintained within The scaffold-free approach results in tissues with poor
the densely populated living matrix by perfusing hyper- mechanical properties and may rely on temporary
oxygenated culture media through printed channels. scaffolding until the tissue is fully mature . Bioprinting-
[12]
Attempts have also been made to endothelialize the lumen assisted tissue emergence allows for spatial and temporal
of these channels with HUVECs, although achieving a control over the introduction of support cells, which play
confluent layer of endothelial cells throughout the entire a crucial regulatory role in the development of organoids,
lumen has not been fully realized. Nonetheless, the results thus enhancing growth and development . Although
[88]
suggest that HUVECs can adhere to the fusing embryonic bioprinting equipment requires considerable precision, this
bodies and remain in place during perfusion. Patent method does not necessitate overly complex bioprinting
channels have been successfully printed into various organ modalities. Instead, the bioprinter is used to accurately
blocks, including compacted embryonic bodies, cerebral and precisely control experimental variables, such as
organoids, and cardiac spheroids, without disrupting the cell density, initial tissue geometry, and the proximity
complex architectures present within these developing and positioning of co-deposited heterogeneous cell
organoids . populations. However, a drawback is that the placement of
[63]
[89]
Suspension-based 3D bioprinting techniques offer spheres in the scaffold is done manually . Interestingly,
unique advantages and challenges. The support bath the development of the bioprinting-assisted tissue
approach utilizing microgel support baths allows for high- emergence technique demonstrates that highly complex
resolution printing and unrestricted diffusion but may printing methodologies are not necessary to strictly
be limited in biomimicry due to the dense nature of the define spatial control over organoid/spheroid deposition.
bioinks. On the other hand, the sacrificial bioprinting Instead, by finding and adjusting suitable conditions
technique, with sacrificial printing into cellular spheroid- between developing organoids and the surrounding
based support baths, enables the generation of complex environment, the geometric complexity of the final tissue
architectures and perfusable vascular networks, but can be achieved through post-printing remodeling and
achieving full endothelialization remains a challenge. Both self-organization. Therefore, bioprinting appears to be best
techniques contribute to the advancement of 3D bioprinting suited as a tool within a design strategy to define initial
in terms of tissue engineering and organ fabrication. conditions and create a favorable environment for the
naturally programmed organoid building blocks and their
relevant support cells to self-organize into specific tissues
3.4. Bioprinting-assisted tissue emergence or organs .
[70]
Bioprinting-assisted tissue emergence aims to enable
the spontaneous formation of larger centimeter-scale 4. Discussion and perspective
multi-cellular organotypic tissues by utilizing bioprinting
to precisely control the initial spatial organization, 4.1. Which is better: scaffold-based or scaffold-free?
texture, and density of the building blocks . As shown Both scaffold-based and scaffold-free strategies should
[88]
in Figure 5D, the bioprinting-assisted tissue emergence be combined. Scaffold-based strategies are preferable for

Volume 9 Issue 6 (2023) 210 https://doi.org/10.36922/ijb.0135