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

manufacturing structurally complex and mechanically
robust MTOs, while scaffold-free strategies are more
suitable for creating biologically scalable constructs that
better mimic native tissue environments. The integration of
both approaches enables the utilization of their respective
strengths and the mitigation of their limitations, thereby
advancing the development of functional multi-cellular
tissues and organoids.
Scaffold-based and scaffold-free strategies are employed
for manufacturing MTOs. Scaffold-based strategies bioprocessing, and automation, achieve a balance between scale, biosafety, printing or self-assembly of tissues and organ samples with high accuracy The printing speed of current devices limits the practical application of fusion
involve using scaffold structures as physical support Integrated biomanufacturing technologies, including 3D bioprinting, Automated biomanufacturing technologies improve and accelerate the The integration of melt electrospinning writing technology and extrusion bioprinting technology creates stable, high-strength, and large-scale lay- strategies, and slow printing speed is an obstacle that needs to be addressed. The process of achieving complex
for guiding cell growth and organization, providing ered structures with spatial distribution of different cell types.
structural integrity, and facilitating the formation of
MTOs architectures. Biocompatible materials are crucial
for scaffold manufacturing to support cell viability .
[90]
While 3D bioprinting offers precise fabrication of complex
scaffold structures and allows for co-printing multiple cell
types and biomaterials, it also has limitations . The limited and resolution. and throughput. multiple cell types.
[91]
availability and performance of biocompatible materials Convergence
and bioinks pose challenges related to ink contamination Good Good Good Good
and toxicity . Furthermore, 3D bioprinting is relatively • • • • • [89]
[92]
slow and can encounter issues like nozzle clogging and
large equipment size due to the complexity of the printing
apparatus .
[93]
On the other hand, scaffold-free strategies aim to create
MTOs without using exogenous scaffolds. These strategies Simplifies manufacturing process Reduces risk of immune response Difficulty in controlling cell distri-
rely on the inherent self-assembly and organization abilities Closer to natural environment Tissue morphology instability Lack of mechanical support
of cells to form functional tissues. Cells are cultured and
allowed to aggregate or undergo spheroid formation,
promoting cell–cell interactions and extracellular matrix Scaffold-free bution
deposition . Scaffold-free approaches offer advantages Bad Good Bad Good • • • • • • [113]
[94]
such as simplified fabrication processes, enhanced cell–cell
communication, and the potential to recapitulate native
tissue organization . The advantages of scaffold-free
[95]
strategies directly address the drawbacks of scaffold-based
strategies. However, they often face challenges in achieving Provides mechanical support Requires additional steps and
precise control over MTOs architecture and may have Controls cell distribution Promotes vascularization Potential immune response May affect cell functionality
limited scalability .
[96]
The choice between scaffold-based and scaffold- Table 3. Comparison of scaffold-based, scaffold-free, and convergence strategy Scaffold-based materials
free strategies depends on the specific requirements Good Bad Good Bad • • • • • • [130]
of the desired MTOs. Scaffold-based approaches are
advantageous for fabricating complex and anatomically
accurate structures, providing mechanical support, and
enabling the incorporation of multiple cell types. In
contrast, scaffold-free strategies offer simplicity, better
mimicry of native tissue microenvironments, and potential Functionalization with biomolecules
scalability for high-throughput applications. Ultimately, Possibility of tissue self-assembly
a combination of both strategies may be employed Mechanical properties
to harness their respective strengths and overcome Initial cell density Disadvantages
limitations, advancing the development of functional Advantages Reference
multi-cellular tissues and organoids. Table 3 summarizes

Volume 9 Issue 6 (2023) 211 https://doi.org/10.36922/ijb.0135