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Table 3. Functional additives used in bioinks
Type of additive Additive Count References
Particles Silicate nanoparticles 6 [167,207,217–220]
Iron oxide nanoparticles 3 [82,151,221]
Bioactive glass particles 2 [222,223]
Other particles 7 [125,196,204–206,208,224]
Biomolecules RGD 14 [199,200,225–236]
VEGF 6 [37,201–203,217,220]
BMP-2 5 [125,237–240]
TGF-b3 4 [125,240–242]
Drugs Rifampin 1 [197]
Daptomycin 1 [197]
Dimethyl-L-oxaloylglycine 1 [198]
Naproxen 1 [243]
Ibuprofen 1 [243]
Atorvastatin 1 [244]
Ropinirole HCl 1 [245]
delivery system [245] to conferring antibiotic [197] and anti- are related to the clinical and market demands (more in
inflammatory [243] activities. line with biomedical/clinical needs instead of what we
New ingredients have been recently added to can accomplish now).
the repertoire of bioink additives to provide relevant Bioprinting technology must attain a more advanced
functionalities for hydrogel-based inks. Examples are the level before facing its most ambitious challenge: the
use of a flexuous filamentous plant virus to enhance printing of functional tissues and organs (i.e., kidneys,
[65]
cell attachment and proliferation in the context of livers, brain organoids, and relevant-sized tumors) to
fabrication of muscle fibers; the incorporation of protease- fulfill the global transplant demands. However, at this
degradable cross-linkers to enable cell remodeling and early stage, bioprinting has already proven useful in
[49]
oxygen-releasing agents to improve and prolong tissue fabricating 3D human biological models for research and
viability [246]
development purposes. We envision that this new market
5. Conclusions of reliable biological models will trigger and amplify the
development of bioprinting and advanced bioinks.
This scientometric analysis of the last two decades of
progress on the use and development of bioinks reveals Conflicts of interest
some very clear trends. Most of the analyzed documents
report the use of simple compositions that fulfill the basic The authors declare that they have no conflicts of interest
requirements of manufacturability and indispensable Acknowledgments
biological performance (cytocompatibility and cell
adhesion). This is consistent with the current stage of We thank MSc. Jessica Janelly Mancilla de la Cruz for
development of bioprinting technology. As with any her assistance in proofreading the manuscript.
emerging technology scenario, bioprinting is naturally
evolving as users address challenges with increasing Funding
degrees of difficulty with the available resources.
However, many of the analyzed documents already This work was supported by Consejo Nacional de
deal with the development of advanced bioinks. This is Ciencia y Tecnología (CONACyT) and Tecnológico
particularly evident in the papers published in the last de Monterrey. S.C.P.G and B.E.P.B acknowledges
5 years. funding received by CONACYT in the form of a
In the future, we anticipate that the scientific reports Graduate Studies Scholarships. G.T.dS, M.M.A,
will deal with a broader and even more specialized and M.R.S gratefully acknowledge the Academic
portfolio of bioprinting technologies, hydrogels, additives, Scholarships provided by CONACyT as members of
and cell sources. We expect to witness an evolution in the the National System of Researchers (Sistema Nacional
field whereby the parameters that guide the bioink design de Investigadores).
International Journal of Bioprinting (2021)–Volume 7, Issue 2 79

