Page 142 - IJB-7-1

Latest Scientific Pathways on Tissue Spheroids: Opportunities to Innovate
Table 1. Tissue spheroid global trends. formation, 135 publications (16%) described the use of
Global trend Description tissue spheroids as building blocks, 100 (11%) relates to
Building blocks Tissue spheroids are used as basic tissue spheroids for drug testing and disease model and
units to biofabricate tissue constructs finally, and 36 (4%) comprise complementary studies of
such as implants organ precursors. tissue spheroids.
Tissue constructs are built placing the Subject areas were identified based on the
tissue spheroids with bioprinting or classification of science disciplines in the Scopus database.
bioassembly techniques. In some cases, For publications indexed in WoS but not in Scopus, their
cells are bioprinted as bioinks to build subject areas were adapted to Scopus categorization to
the final tissue construct, but before maintain homogeneity. In this study, the analysis of all
its completion, cells first aggregate in 868 publications revealed nine subjects following the
spherical forms before they fusion distribution displayed in Figure 2: biochemistry, genetics
Drug testing and Cell aggregates are used as a 3D culture and molecular biology (25%), engineering (19%),
disease model model for drug testing purposes or for materials science (16%), chemical engineering (11%),
mimicking a particular disease. The medicine (10%), chemistry (4%), immunology and
resulting model can be formed by a microbiology (3%), applied physics (3%), and other (9%).
single tissue spheroid or by a tissue However, biochemistry, genetics and molecular biology,
construct product of the fusion of engineering, and materials science account for more than
several tissue spheroids made of one or half of all the publications with 60% of all the documents.
different cell lines The growth dynamics of publications on tissue
Spheroid This category is related to the spheroids were defined as shown in Figure 3. In terms
formation improvement of the tissue spheroid of publications, number of papers by year of publication
formation, particularly to uniform the did not exhibit a strictly patterned behavior (e.g., linear
tissue spheroids characteristics (i.e. or exponential); nevertheless, publications regarding
size and cells number) and to scale up tissue spheroids showed an increased growth from 2
the process for mass tissue spheroid publications in 2000 to 122 publications in 2018. The
formation. But no specific applications year 2019 was not depicted in the graph since the retrieval
were discussed in documents analyzed period ended on June 5; thus far there had been 42 overall.
Complementary Complementary studies for tissue The biggest growth was seen from 2015 to 2016, with a
studies spheroids management, such as the 35.5% increase, going from 76 documents to 103. Of the
development of computer programs and 868 scientific documents, 51% were published in the past
mathematical models to simulate tissue 5 years (2015–2019).
spheroids behavior, and the production The affiliations of authors indexed in high-impact
of novel accessories for imaging scientific databases are an indicator, of which countries
systems for tissue spheroids monitoring and organizations have patterns of research concentration.
The top countries and cities with the largest numbers of
scale resolution that emulate the extracellular matrix publications on tissue spheroids were also determined;
(ECM) of human tissues/organs and improving the speed results are presented in Figure 4A and B. The United
for fabrication of human-scale tissues/organs. States is the most prolific country with 288 publications,
Ashammakhi et al. published on the challenges followed by Japan with a total of 155, China with 93, and
[3]
involving multicomponent bioinks that are related to Germany with 84 published articles. These four countries
account for more than half (55%) of the total documents.
the development of appropriate materials having shear- The remaining countries on the top ten published between
thinning properties with cell-friendly capability and 26 and 73 scientific articles and are located either in
other desired biological characteristics for different western Europe or eastern Asia – except for Canada,
tissue engineering applications. As Ng et al. indicate, which holds the ninth position.
[5]
it is also important to know more about the composition The top cities are highly correlated with the top ten
and spatial arrangement of living cells and ECM within countries; however, the rankings are much closer in the
tissue constructs along with the development of advanced total output, except Seoul, with 57 and Tokyo with 46
bioprinting strategies. scientific documents which have almost twice as much
3.2. Scientometric analysis results as the output from other cities in the top ten. We can
conclude that a significant amount (78%) of the papers
As shown in Figure 1, of the 868 publications obtained, produced in South Korea are centralized in Seoul, whilst
597 publications (69%) exhibited the analysis of spheroid in Japan, most of the papers were contributed from four

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