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even larger tissue constructs. Due to the inherent lack of filler material, these strategies enable

engineering of artificial tissues at highest cell densities. Notably, the complete absence of a
scaffold can potentially complicate handling, logistics (i.e., long-term viability), lack of

protection from mechanical damage, and notably also hampers the dynamic and precise control
the mechanical construct properties.

A convergent approach was recently introduced as the third strategy of modern TE that builds

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upon the synergistic advantages of scaffold-based and scaffold-free approaches . In this
approach, spheroids are reinforced through highly-porous microscaffolds that act as protective

cage. The so-formed scaffolded spheroids (S-SPHs) then act as building blocks for larger
tissues, since they still have the inherent capability to fuse with neighboring building blocks.

Based on the material properties and the design of the microscaffold, the resulting mechanical
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properties can be controlled accoordingly .

The formation of such building blocks requires the presence of a microscaffold during the

spheroid formation process. Given the general molecular diffusion limits present in tissue
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engineered constructs , these structures should not exceed 300 µm in diameter. Recently, our
group demonstrated how highly porous cage-like microscaffolds, also referred to as buckyballs
(BBs) due to the similarity with Buckminster fullerene, were used to contain spheroids to form

building blocks that were able to fuse together via directed self-assembly. However, to form a

tissue of a relevant size out of such scaffolded spheroids (S-SPH), the formation of at least
several thousands of such building blocks is required. For this, the antiadhesive multi-well cell

culture plates have to be filled with precisely one scaffold per each well. While the manual
deposition of microscaffolds and cells is possible, it’s a tedious process that cannot be scaled

indefinitely and further does not allow efficient pre-screening of the microscaffolds for quality

control (i.e., structural integrity).

To reproducibly form uniform S-SPHs, an intact microscaffold must be placed into a single

well, followed by the deposition of a determined cell number. The whole process must be
scalable to support the recurring formation of a large amount of such building blocks.

Microfluidic devices have previously shown great promise for precise control and manipulation
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of particles in flow . However, most examples in the literature typically employ microfluidic
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devices to diverge an inlet flow into two or more collecting channels . While this allows
continuous physical separation, such systems cannot be used to eject particles one-by-one.
Only recently, systems were described that allowed the continuous ejection of fluidic droplets

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