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Rodriguez-Salvador, et al.
identification of keywords and the design of a search the technological application of the tissue spheroids
query as accurately as possible is required; thereby, it mentioned previously.
involves expert consultation from the beginning through A scientometric analysis was applied to the
the validation of the final results . Hence, the search collected data to identify the current and emerging areas
[19]
query of this study was developed through an iterative of tissue spheroids applications. First, subject areas were
process, to identify additional keywords, aside from the identified according to the classification given by Scopus.
ones provided initially by experts on the topic, to improve For publications indexed in WoS but not in Scopus, their
its accuracy. The general structure of the search query subject areas were adapted to Scopus classification to
employed is as follows: maintain homogeneity. Subsequently, the publishing
((( spheroid* PRE/1 ( cell OR cellular )) OR ("3 growth dynamics within the time range selected (January
d spheroid") OR (( 3d OR "three dimensional" OR "3 1, 2000, to June 5, 2019), along with the most prolific
dimensional" OR "three d") PRE/1 spheroids ) OR ( countries, cities, authors, journals, and institutions on
cancer PRE/1 spheroids ) OR ( tumor* PRE/1 spheroids ) the topic were identified. Finally, a cluster analysis was
OR ( tumorspheres OR tumourspheres OR tumorospheres performed to determine networks of collaborations
) OR ( cell* PRE/4 spheroid*) OR ( multicell* PRE/3 between institutions and authors.
spheroid*) OR ( tissue* PRE/2 spheroid*) OR (( hepat*
OR liver OR pancrea* OR thyroid OR organotypic OR 3. Results and discussion
cardiomyocyte ) PRE/0 spheroid ) OR ("self assembl* A total of 1296 scientific documents published between
spheroid") OR cardiosphere OR ( cell AND ( spheroid January 1, 2000, and June 5, 2019, were retrieved; 783
PRE/0 ( formation OR invasion OR culture )))) AND from Scopus and 513 from WoS. A deduplication and
("tissue engineering" OR "regenerative medicine") AND manual validation process was performed, resulting in
NOT ( plant OR graphite OR bacter* OR alga* OR "solar 868 publications. These publications were classified
cell*" OR "eutectic cell*" OR yeast OR spheroidin OR according to the following categories.
alloy OR rhodopseudomonas OR phytoplankton OR
mycobacteria OR larva OR protista OR volvox OR coli 3.1. Global trends
OR "non-spheroid*" OR anisotropic OR pollen OR coral Scientific articles and conference papers retrieved in
OR biofilm OR sponge OR plankton OR microalga* this study revealed four global trends depending on
OR dictyostelium OR microbial OR microbe OR the application given to tissue spheroids. These are
phytoplankton OR saccharomyces OR eps OR candida building blocks, drug testing and disease model, spheroid
OR sea OR food OR amoeba OR "date palm" OR kelvin formation, and complementary studies. Each category is
OR peanut OR lanata OR yew OR roseus OR ajuga OR described in Table 1. The following tables (Tables 2-5)
"protein aggregates" OR antenna OR batter* OR foam correspond to the most recent and representative studies
OR barnacle OR oblate OR review OR overview )) from the documents analyzed for each global trend.
Boolean operators AND, OR and NOT were Results of these tables show the specific focus of the
used to include and exclude the terms and the PRE/# different group trends identified. There is a diversity of
function that indicates the number of words that may bioinks and cell types, ranging from healthy cells, such
be close to a specific term. Scopus and Web of Science as human fibroblasts, human umbilical vein endothelial
(WoS) databases were selected to collect the scientific cells (HUVECs), human mesenchymal stem cells from
documents. Scopus contains more than 5000 publishers bone marrow (hMSCs), human-induced pluripotent cells
and 75 million items indexed dating back to 1970 (hPCSs), and carcinogenic cells (e.g., human breast cancer,
across different disciplines in science . In addition, osteosarcoma, colon carcinoma, hepatoma, and ovarian
[20]
WoS includes scientific documents from over 21,000 cancer cells). Among them, the HUVECs, MSCs, and
high-impact journals covering more than 100 years of PCSs are the most used cell types. For example, stem cells
scientific production . offer interesting advantages as they can be obtained from
[21]
Gathering scientific documents were conducted various sources and differentiated into various lineages .
[3]
for journal articles and conference papers from both Our findings also exhibit that there is no single
databases that were published between January 1, predominant 3D bioprinting process, this technology is
2000, and June 5, 2019 (when the collection activity evolving rapidly and different approaches exist depending
ended). The documents obtained from each database on the main goal to achieve. Moreover, our results
were exported and combined into a single list, where also show that spheroid resolution can be manipulated
a manual cleaning process was performed to remove depending on the purpose of the study provided that a
documents not complying with the purpose of the study, certain spheroid size is not yet defined.
as well as those containing duplicated information. According to Ng et al., a key dilemma lies in the
[5]
The resulting documents were classified according to need of obtaining a balance between achieving the nano-
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