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parallel to easily boost the throughput further, making this approach highly adaptable for future

high-throughput bioprinting workflows.

As expected, the cellular metabolic activity decreased when in the automated deposition

because of the exposure to high shear stresses in comparison to the manually deposited
ones(Figure 7 c).While the dispensing process shown here was not directly comparable to

FACS, other studies have shown that depositing cells using FACS showed a comparable

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negative influence on their viability and proliferation , most likely caused by cleavage of
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membrane proteins that triggered further stress-related pathways .

As shown in Figure 7d, the type of well plate had an important influence on the formation of
spheroids within microscaffolds. High-density well plates with a V-shaped bottom and a low-

retention coating would provide the perfect culture conditions. However, the latter two

parameters were typically exclusive features on commercially available well plates. Therefore,
low-retention coatings were manually applied on V-shaped plates to increase the formation of

spheroids.

Unlike hydrogel-based microparticles, which often suffer from low mechanical strength and

deformation under shear stress, scaffolded spheroids combine high cell density and natural

cell–cell interactions with a rigid, porous microscaffold that provides mechanical stability,
protection, and tunable properties, enabling their use as modular building blocks for larger

tissues

Conclusions

The third strategy for tissue engineering encompasses the formation of a spheroid within a

highly porous microscaffold that shields the spheroid form mechanical impact, as well as
enabling its fusion with surrounding scaffolded spheroids (S-SPHs), precisely controlling the

formation of individual building blocks for the bottom-up fabrication of larger tissue blocks
that in turn better resemble the scale of actual human tissues. While discussed for bottom-up

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TE elsewhere , in this work we have focused on solving the limitations arising when
fabricating a significant amount of such building blocks for technological scale-up for mass
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production . Automating particle analysis, sorting and dispensing steps supported by the
interplay of microfluidics for fluid transportation and actuation, as well as optical elements for

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