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

the characteristics of scaffold-based, scaffold-free, and to help guide the development of microtissues and self-
hybrid strategies and provides a qualitative comparison organizing structures [103] . It can provide a careful balance
in terms of initial cell density, mechanical properties, the between engineering guidance and dynamic remodeling
possibility of tissue self-assembly, functionalization with within a developing organization if designed and
biomolecules, advantages, and disadvantages. implemented. Successful tissue-guided implementation
can have significant implications for the engineering of
4.2. Convergence strategy and hybrid biofabrication spatially complex tissues such as articular cartilage, where
techniques controlling the structure of collagen networks remains a
The convergence strategy integrates scaffold-based and crucial challenge in the field.
scaffold-free strategies to achieve a balanced biofabrication
scale, biosecurity, and resolution. This is accomplished For the first time, in vitro research was carried out on the
through the utilization of hybrid biofabrication combination of melt near-field direct writing technology
technologies, including 3D bioprinting, bioassembly, and and multi-cellular spheroids, which can produce high-
automation. 3D bioprinting is employed for manufacturing precision fiber structure scaffolds up to 2 μm, and
extracellular matrix or basic assembly modules, while biological scaffolds constructed by melt near-field direct
assembly techniques are employed to position the modules writing technology have the advantages of easy operation
and complete the target object. Automation technology is and visualization [104] . Moreover, it is reported that when
implemented to replace manual operations, reduce errors, the size of the spheroid and the scaffold pore match, the
and enhance production efficiency. survival rate can reach 90%. Integrating the advantages of
vacuum adsorption and suspension-bath printing, a high-
Automated biofabrication techniques enable resolution method was developed to transfer spheroids into
convergence strategy, allowing to print the specific self-healing support hydrogels, thus patterning them and
scaffold structures required for organoids with high fusing them into high-cell density microtissues at pre-set
accuracy and throughput. Better and faster printing or spatial locations [105] , successfully printed an iPSC-derived
self-organization of tissue or organoids can be achieved cardiac microtissue model with spatially controlled and
with automated biofabrication techniques. In addition, proportional cardiomyocytes and fibroblasts to mimic the
stem cell suspensions can self-organize into millimeter- structural and functional properties of scarring cardiac
scale structures and be further printed into more extensive tissue triggered after myocardial infarction, including
and complex MTOs, using the resulting geometry scaffold decreased contractility and irregular electrical activity.
structure to guide organoid formation [18,97] . Integrating
melt near-field direct writing technology and extrusion Slow printing is an obstacle that can be overcome.
bioprinting technologies creates stable, high-strength, The performance of the current equipment used for
large-size hierarchies utilizing the spatial distribution printing stands is bottlenecked in terms of speed. Even
of different cell types . Fibers with 500 nm–100 μm with the advanced two-photon polymerization (2PP)
[98]
diameters and complex pattern deposition were prepared printer developed by Faraji Rad et al. [106] , it is about 100
using melt input direct writing and melt near-field direct times faster than any commercially available device. The
writing technology . required small bracket will also take more than 37 h to fill
[99]
a 5-mm deep cylinder with a diameter of 5 mm . Slow
[89]
The emerging convergence strategy represents a printing can be solved by storing materials, scaffolds, and
convergent research direction with the potential to enable aggregate spheroids in advance, or scaffold fabrication and
disruptive solutions and advance the field of tissue function bioassembly can be carried out simultaneously through
and regenerative medicine . Fabrication of modules for fusion strategies.
[89]
bioassembly, such as aggregate spheroids, tissue blocks,
and scaffolds, is carried out separately and independently A method is being developed, known as BMMm, which
to avoid damage to cells . It is thought that by changing aims to achieve a patterned arrangement of heterogeneous
[89]
the nature of the temporary scaffold or module used for aggregate spheroids in 3D space. This method has the
assembly, the system can be optimized for different cell potential to construct large-scale (centimeter) tissues
and tissue types, resulting in the construction of more or organoids with intricate structures, as demonstrated
complex and functional MTOs. 3D bioprinting should in Figure 6. This method includes micromesh patterns,
be used to create complex microenvironments, not just to different types of aggregate spheroids, and other auxiliary
build cell structures [100] . A scaffold-free strategy has been devices, such as temperature monitoring sensors and
reported to successfully construct structures with curved oxygen delivery pipelines. Preparing complex bioink is
surfaces and vascular-like structures [101,102] . Scaffolds and unnecessary in BMMm, and aggregate spheroids are the
microstructural devices can provide a valuable platform primary assembly unit, maintaining the advantage of a

Volume 9 Issue 6 (2023) 212 https://doi.org/10.36922/ijb.0135