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Latest Scientific Pathways on Tissue Spheroids: Opportunities to Innovate
           Table 4. Global trend: Spheroid formation.
           Article                       Year/Journal    Impact Analysis
           Miller, A. J. et al. “Generation   2019/Nature   “Protocol that recapitulates several stages like induction,
           of lung organoids from human   Protocols      patterning, lung specification, budding, morphogenesis; to
           pluripotent stem cells in vitro” .            differentiate human pluripotent stem cells (hPSCs) into ventral–
                                    [28]
                                                         anterior foregut spheroids and further into two distinct types
                                                         of organoids: human lung organoids and bud tip progenitor
                                                         organoids.”
           Lee, W. et al. ” Dispersible   2019/Nature    “Development of ultrasoft mechanosensors that visibly deform
           hydrogel force sensors reveal   Communications  under <10 Pascals of cell-generated stress. By incorporating
           patterns of solid mechanical                  mechanosensors into multicellular spheroids, the patterns
           stress in multicellular spheroid              of internal stress that arise during spheroid formation where
           cultures”                                     captured. This technique can provide a quantitative basis to
                  [29]
                                                         design tissues that leverage the mechanical activity of constituent
                                                         cells to evolve towards a desired form and function.” In this
                                                         research, HS-5 fibroblasts were used as well as an aqueous two-
                                                         phase droplet printing technique by an automated liquid handler
                                                         in a concentration of 6×107 cells/mL.
           Heo, D. N. et al. ” Synergistic   2019/Acta   “To enhance stem cell function and generate pre-vascularized
           interplay between human MSCs   Biomaterialia  network, a collagen/fibrin hydrogel was employed as
           and HUVECs in 3D spheroids                    an encapsulation matrix for the incorporation of human
           laden in collagen/fibrin hydrogels            mesenchymal stem cell/human umbilical vein endothelial cell
           for bone tissue engineering” [30]             (MSC/HUVEC) spheroids, and their cellular behavior (including
                                                         cell viability, morphology, proliferation, and gene expression
                                                         profile) was investigated and compared to that of cell suspension-
                                                         or MSC spheroids-laden hydrogels.” In this study, microwells
                                                         in AggreWell plates were used. Cell suspension at a density of
                                                         1.2×106 cells/well was seeded. MSC-only and MSC/HUVEC
                                                         (75%/25%) spheroids were used.






















           Figure 1. Distribution of scientific publications by categories.

           authors were Vladimir Mironov and Vladimir Kasyanov   Figure 2. Distribution of the subject areas of publication on the use
           with 24 and 14 publications each. The third most prolific   of tissue spheroids.
           author is Gerhard Björn Stark with 13 scientific articles.
           These  findings  can  correlate  directly  to  the  recently   made  by  Russian  bioprintists  that  have  contributed  to
           published paper “Bioprinting in the Russian Federation:   global technology in the field, such as the development
           Can Russians Compete?” by Peter Timashev and Vladimir   of original 3D bioprinters, natural bioinks and the world’s
                                                                                                      [34]
           Mironov  in  which  they  state  five  main  achievements   first functional and vascularized organ construct .


           140                         International Journal of Bioprinting (2021)–Volume 7, Issue 1
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