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Uncovering 3D bioprinting research trends: A keyword network mapping analysis

           each keyword.                                       table 3. Most frequent terminology for materials, biological
            In order to identify trends of research on 3D bio-  components, and applications in papers analysed from APY 2011
                                                               to 2016.
           printing the APY of the keywords contained on the
                                                                   Most frequent
           network map was determined. This was obtained       aPY keywords   Material   Biological   application
                                                                                         component
           by averaging the publication years of each article      (Occurrences)   (Occurrences)  (Occurrences)   Occurrences)
           containing each keyword. Results showed that the APYs             ‘PLGA’                 ‘Bioengineered
           ranged from 2002 to 2016. However, for co-occurrence   2011  ‘Cell Sheet’  (25)  ‘Bone Marrow’  Construct’
                                                                   (148)
                                                                                         (44)
           analysis, APYs of only 2011 to 2016 were considered as                                   (20)
           the majority of keywords (67% of 1,759) were found in   2012  ‘Expression’  ‘Biopolymer’  ‘Progenitor Cell’  ‘Bone Tissue
                                                                                                    Engineering’
           these years.                                            (212)     (52)        (60)       (153)
            Figure 2 shows the co-occurrence network maps          ‘Treatment’  ‘Hydroxyapatite’  ‘Mesenchymal ‘Vascular
           obtained for each APY from 2011 to 2016; again, the   2013  (235)  (33)       Stem Cells’   Network’
                                                                                         (188)
                                                                                                    (69)
           keywords are represented by nodes and are connected by   ‘Bone                           ‘Bone
           links. Number of keywords and links are shown in Table   2014 Regeneration’  ‘PLA’  ‘MSCs’   Regeneration’
                                                                             (56)
                                                                                         (54)
           2.                                                      (112)                            (112)
                                                                   ‘Spheroid’  ‘GelMA’   ‘Pluripotent  ‘Cartilage
                                                               2015                       Stem Cells’   Repair’
           table 2. Number of keywords and links by average publication   (127)  (37)    (31)       (28)
           year (APY)                                                        ‘Photocurable
                                                               2016  ‘Bioink’   Resin’   ‘IPSC’     ‘Organoid’
                                                                                         (18)
                                                                                                    (24)
                                                                   (230)
            aPY           Number of keywords   Number of links               (6)
                                           1,825
            2011          207                                  years (2015–2017). The results obtained indicated that
                                                               studies on treatment were primarily focused on cancer,
            2012          279              4,231
                                                               regenerative medicine, and MSC analysis. The keyword
            2013          303              4,386               ‘Treatment’ was also related to other keywords such
                                                               as ‘Osteochondral Defect’, ‘Implant’, ‘Medicine’, and
            2014          203              1,233               ‘Bone Defect’. By contrast, ‘Bioink’, a fundamental
                                                               element in bioprinting, was mainly found in relation
            2015          148              620                 to multicellular spheroid deposition for guaranteeing
                                                               maximal cell density [17,19,29,30]  as well as in relation to
            2016          53               66
                                                               hydrogels (e.g., ‘gelation’ and ‘GelMA’ or ‘Gelatin
                                                               Methacryloyl’) and ‘Cell Sheet’ and ‘Printability’, which
            The keywords for APY 2011 to 2016 were analysed    are crucial factors in the fabrication of living tissue.
           to determine which of them dominated the discussion   Additionally, to identify the predominant keywords
           of 3D bioprinting materials, applications, or methods   in papers published in the last three years (2015–2017),
           during these years.                                 the APY 2016 was analysed; the identified terminology
            Table 3 shows the results of the most frequent     can be considered to reflect recent research efforts in
           terminology for materials, biological elements, and   bioprinting. The results showed that the keyword ‘Bioink’
           applications for each of the APYs analysed (APY 2011–  occurred most frequently (230 occurrences) followed
           2016). The most frequent keyword was ‘Treatment’ with   by ‘Organoid’ and ‘ADSC’ or ‘Adipose Tissue-Derived
           235 occurrences in APY 2013. For materials, the most   Stem Cells’ (24 occurrences each); ‘Cell Spheroid’ (19
           frequent keyword was ‘PLA’ (Polylactic acid) with 56   occurrences); ‘GelMA’ (9 occurrences); and ‘Calcium
           occurrences in APY 2014. For biological elements, the   Ion’, ‘Concave Microwell’, and ‘Integrin Binding’ (7
           most frequent keyword was ‘Mesenchymal Stem Cells’   occurrences each). Four of these keywords (‘GelMA’,
           with 188 occurrences in APY 2013; furthermore, it was   ‘Calcium Ion’, ‘Concave Microwell’, and ‘Integrin
           found as ‘MSCs’ with 54 occurrences in APY 2014. For   Binding’) are directly related to bioprinting with cell
           applications, the most frequent keywords were ‘Bone   spheroids for the retention of 3D cellular structures .
                                                                                                            [30]
           Tissue Engineering’ with 153 occurrences in APY 2012   In terms of applications, the most frequent keyword was
           and ‘Bone Regeneration’ with 112 occurrences in APY   ‘Drug Development’ (12 occurrences), which reflects
           2014.                                               one of the emerging applications of bioprinting [1,9,22] .
            From a general perspective, from APY 2011 to 2016,   Finally, a specific outlook of bioprinting trends was
           the most frequent keywords were ‘Treatment’ (in APY   developed by considering the following elements:
           2013) and ‘Bioink’ (in APY 2016), indicating that these   bioprinting techniques, cell sources, and tissue/organs.
           terms have been widely researched for the past three   For this task, a keyword analysis of previously identified


           4                           International Journal of Bioprinting (2018)–Volume 4, Issue 2
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