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Discovering new 3D bioprinting applications: Analyzing the case of optical tissue phantoms
           Table 5. Global trends for optical tissue phantoms development using 3D printing
           Category  Trend
           Methods  Spin coating process predominates because this technique allows thin layers to be generated (30–60 µm in thickness), which better mimic
                    the layer structure of biological tissues
           Materials  Polydopamine, polydimethylsiloxane, and the hydrogel, PVA, are present to elaborate matrix tissue phantoms. To mimic scattering properties, TiO   2
                    powders, intralipids, and PVA (involving a freeze-thaw treatment) are used. Finally, those applied to mimic absorption properties include India ink,
                    dyes, graphite powder, hemoglobin solutions, and coffee
           Uses     Applications are divided into the following:
                     Diagnosis techniques, specifically: (1) Medical imaging procedures: confocal microscopy, optical coherence tomography, optical diffusion tomography,
                     hyperspectral reflectance imaging, fluorescence imaging and photoacoustic; and (2) spectroscopy (diffuse reflectance and near-infrared spectroscopy); and
                     Phototherapy techniques, especially in tests for tattoo removal using laser
           PVA: Polyvinyl alcohol, 3D: Three-dimensional
           the predominant materials for the matrix of 3D printed   both  scientific  papers  and  patents  in  the  field  - Purdue
           optical tissue phantoms include both polymers and   University and Georgia Institute of Technology, both in
           hydrogels since they facilitate the addition of other   the United States and Pukyong National  University in
           substances to improve the optical properties of the   South Korea. Specifically, a quarter of the total scientific
           phantom [31]  and can be used easily for 3D printing [16,51] .   papers identified was published in the proceedings of the
           Materials of non-biological origin (TiO , India ink, dyes,   SPIE.
                                            2
           graphite powder, and PVA) are preferred over biological   Regarding limitations, this research was restricted by
           materials (such as intralipid and hemoglobin solutions).   a lack of information, due to the novelty of applying 3D
           Finally, two categories of phantom applications were   printing in the development of optical tissue phantoms.
           identified, namely diagnosis and phototherapy, with the   This  issue  led  to  obtaining  few  scientific  papers  and
           first  predominating;  the  dearth  of  research  on  optical   especially patents, and it was not possible to identify a
           tissue phantoms for phototherapy may be because     clear trend of the behavior of patents published in this
           phantoms do not yet possess thermal properties and   field.  In  terms  of  3D  bioprinting,  no  documents  using
           dynamics like blood flow in tissue, which is crucial for   this technique to produce optical tissue phantoms were
           phototherapies [64] . However, efforts are being made to   detected, which limited the study to analyzing publications
           develop  phantoms  that  include  vascular  tissue  filled   on 3D-printed phantoms.
           with blood or hemoglobin solutions to mimic the tissue   Since the applications  of both 3D printing  and 3D
           oxygenation and blood perfusion [31,54,65] .        bioprinting are growing, future analysis will be based on
                                                               a higher number of publications, especially for the latter.
           4 Conclusions                                       Indeed,  3D bioprinting  is already  utilized  to produce
           In this study, scientometric and patentometric analyses were   phantoms, but in other areas, such as ultrasound imaging,
                                                                                                  [63]
           carried out to identify trends in the use of 3D printing or 3D   where they are known as “biophantoms” . Ultimately,
           bioprinting to develop optical tissue phantoms, focusing   3D printing technology has a disruptive potential for the
           on the following key elements: Methods, materials, and   development of optical tissue phantoms; this technology
           uses, as well as predominant countries, institutions, and   has distinct  advantages  over traditional  methods, such
           journals. The results revealed that 3D printing is already   as the development of complex multilayered structures,
           used for the development of optical tissue phantoms, where   easy production, and low cost. Unique biophotonic
           the spin coating is the most frequently employed method.   prototypes  can  be built  using 3D bioprinting,  thereby
           Materials such as polymers and hydrogels prevail as the   facilitating diagnosis tests, equipment validation, and so
                                                                 [66]
           phantom matrix; meanwhile, to mimic optical properties,   on . The 3D bioprinting domain is still in development,
           the use of synthetic materials such as TiO , India ink, or   and its uses and applications  in many areas have not
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           dyes outweighs that of biological materials (intralipids,   been completely studied, so this research reveals a new
           hemoglobin, etc.). Finally, it was identified that 3D printed   window of opportunity to explore.
           optical tissue phantoms are mainly focused on diagnostic   Conflicts of Interest
           purposes rather than phototherapy.
             The insights obtained in this study illustrate that the   No conflicts of interest are reported by the authors.
           more active countries in R&D on optical tissue phantoms
           using 3D printing are the United States and China. The   References
           main institutions that publish scientific papers in this area
           are located in the United States; meanwhile, in terms of   1.   ASTM F2792-10, 2010, Standard Terminology for Additive
           patents, the leading institutions come from South Korea.   Manufacturing  Technologies.  West Conshohocken, PA:
           Only three  institutions  were detected  that  published   ASTM International. https://www.astm.org.

           8                           International Journal of Bioprinting (2019)–Volume 5, Issue 1
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