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Rodriguez-Salvador, et al.
Table 5. Global trend: tissue spheroids as building blocks applying biofabrication techniques.
Article Authors Year/Source Impact Analysis
Accessible Reid, JA; Mollica, 2016/ To the best of the author’s knowledge, their system is
bioprinting: PA; Johnson, GD; Biofabrication the first “3D printed, bioprinting system” to reliably
Adaptation Ogle, RC; Bruno, achieve single-cell print resolutions within 50.0 µm
of a low-cost RD; Sachs, PC. resolution while also exerting minimal unwanted
3D-printer for impact on the cells viability and post-printing fate.
precise cell The plotting routine was set to dispense a number of
placement 100 nL droplets 200.0 µm (X, Y) apart and 250.0 µm
and stem cell (Z) from the plate bottom into wells of a 96 well plate
differentiation [25] containing 50.0 µL of a 1:1 mixture of growth factor
reduced Geltrex and differentiation supportive media.”
The human induced pluripotent stem cells (hiPSC)
“aggregates were incubated at 37.0°C, 5.0%CO for
2
7 days. […] an accessible open-source 3D bioprinter
capable of serving the needs of any laboratory
interested in 3D cellular interactions and tissue
engineering.”
Airflow-Assisted Zhao, H; Chen, Y; 2018/Small “[…] heterogeneous microspheroids are drawing much
3D Bioprinting Shao, L; Xie, M; attention as a promising tool to carry multiple cell
of Human Nie, J; Qiu, J; Zhao, types in separated phases […] a novel airflow-assisted
Heterogeneous P; Ramezani, H; Fu, 3D bioprinting method is reported, which can
Microspheroidal J, Ouyang, H; He, Y. print versatile spiral microarchitectures inside the
Organoids with microspheroids.” Printed spheroids presented a 0.5 mm
Microfluidic diameter with an inner spiral of 10.0 µm. L929 cells
Nozzle [27] were cultured for 4 days and had a 90.0% viability
Magnetic Labusca, L; Herea, 2021/Journal In this study, the authors used magnetic levitation
nanoparticle DD; Minuti, of Biomedical to “obtain highly reproducible human ADSC–MNP
loaded human AE; Stavila, C; Materials assembled in 3D culture (spheroids) with the purpose
adipose derived Danceanu, C; Research Part of increasing stem cell specific properties. […]
mesenchymal Grigoras, M; B: Applied Levitated spheroid culture of ADSC-MNP can be
cells spheroids Ababei, G; Chiriac, Biomaterials further tested for various application in regenerative
in levitated H; Lupu, N. medicine and organ modeling.” Adipose-derived
culture [49] mesenchymal cells (ADSC) spheroids were combined
with magnetic nanoparticles (MNP) and cultured
in a 96 well plates with a concentration of 1000
cells at 37.5°C for 7 days. “For magnetic field (MF)
stimulation and establishment of levitated culture,
permanent NdFeB magnets with diameter of 8 mm
each were placed on the top of the 96 well plate and
incubated.”

5. Conclusion building blocks: Seeding and Biofabrication. At present,
manual seeding predominates over the automated
A scientometric analysis as part of a CTI process was
carried out to determine the scientific research dynamics process of biofabrication, however, with the arrival of
of tissue spheroids as building blocks. To accomplish this, digitalization, it is expected that new technologies such
scientific publications were retrieved from Scopus for the as artificial intelligence and robotics will be incorporated
period between January 1, 2015, and December 31, 2021, in the future, providing more robust processes and tissues
then organized and analyzed. The results revealed that the with superior performance. To describe the overall
application of tissue spheroids as building blocks is still research publications landscape and specific trends for
at an early stage. During our research, publications were seeding and biofabrication methods, the subject area
classified into two fundamental categories based on the distributions, the most prolific countries, cities, journals,
techniques used to deposit or assemble tissue spheroids as and institutions, and the most cited articles regarding this

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