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International Journal of Bioprinting 3DP hydrogels to combat antibiotic-resistant bacteria
Rif acts by interacting with the b-subunit of the bacterial TECHMATSTRATEG2/407770/2/NCBR/2020 entitled
RNA polymerase encoded by the rpoB gene. Rif resistance New functional MATerials for 3D printing in UROlogy
is acquired through key amino acid substitutions in the needs, acronym MATURO 3D.
b-subunit leading to a reduced affinity to the antibiotic [50,51] .
In our case, the rpoB gene from our S. aureus RN4220 Rif Conflict of interest
resistant isolates cultured from the Rif hydrogels had three The authors declare no conflicts of interest.
SNPs known to cause resistance to Rif . On the other
[42]
hand, S. aureus AMC 201 isolate exposed to GelMA-Rif- Author contributions
NPs hydrogel showed resistance to Rif but did not have
any mutation in the rpoB gene region studied. To the best Conceptualization: David Martínez-Pérez, Clara Guarch-
of our knowledge, there have been no other resistance Pérez, Martijn Riool, Sebastian A. J. Zaat, Wojciech
mechanisms to Rif reported for S. aureus [52,53] . However, Święszkowski
referring to the mechanism of resistance development to Funding acquisition: Sebastian A. J. Zaat, Wojciech
other antibiotics such as ciprofloxacin, this could be due to Święszkowski
an increased expression of efflux pumps . Investigation: David Martínez-Pérez, Clara Guarch-Pérez,
[10]
Muhammad Abiyyu Kenichi Purbayanto
5. Conclusions Project administration: David Martínez-Pérez, Clara
Guarch-Pérez
The double antibiotic-loaded GelMA hydrogels (GelMA- Resources: Sebastian A. J. Zaat, Wojciech Święszkowski
Rif-Van-NPs) show promising in vitro outcomes as an Supervision: Emilia Choińska, Martijn Riool, Sebastian A.
antimicrobial drug delivery system to prevent or treat J. Zaat, Wojciech Święszkowski
implant-related infections. In this work, we showed that Visualization: David Martínez-Pérez, Clara Guarch-Pérez
3D-printed GelMA hydrogels containing antibiotic-loaded Writing – original draft: David Martínez-Pérez, Clara
PLGA NPs allows for the design of a combined, controlled, Guarch-Pérez
and gradual release system for two antibiotics, which Writing – review & editing: Martijn Riool, Sebastian A. J.
can be used to prevent the development of antimicrobial Zaat, Wojciech Święszkowski
resistance. In the future, depending on the needs of the
patient, this system may be modified to accommodate All authors have read and agreed to the published version
various implant types, geometries, and antibiotics. of the manuscript.
Acknowledgments Ethics approval and consent to participate
Not applicable.
We would like to thank Dr. Nehar Celikkin for her technical
support in synthesizing gelatin methacrylate and the 3D Consent for publication
printing process. We would like to thank Mariusz Nyc
for technical support in rheological analysis. We would Not applicable.
like to thank Stefany Alonso for her technical support in
development of models in 3ds Max Autodesk. We would also Availability of data
like to thank Dr. Nicole van der Wel (Electron Microscopy Data can be requested from David.perez@pw.edu.pl .
Center Amsterdam [EMCA], Amsterdam UMC) for her
technical assistance in collecting the SEM images. We would Further disclosure
like to thank the Core Genomic Facility of the Amsterdam
UMC, Amsterdam, the Netherlands for their technical Some preliminary results were presented at European
support with sanger sequencing. Benchling Biology Software Society for Biomaterials 2018 and Biofabrication 2018.
(2022) was retrieved from https://benchling.com.
References
Funding 1. ter Boo G-JA, Grijpma DW, Moriarty TF, et al., 2015,
This work was funded by the research project PRINT- Antimicrobial delivery systems for local infection
AID within the EU Framework Programme for Research prophylaxis in orthopedic- and trauma surgery. Biomaterials,
52:113–125.
and Innovation Horizon 2020 – Marie Skłodowska-
Curie Innovative Training Networks under grant https://doi.org/10.1016/j.biomaterials.2015.02.020
agreement No. 722467 and by the National Centre 2. Masters EA, Trombetta RP, de Mesy Bentley KL, et al., 2019,
for Research and Development under the grant no. Evolving concepts in bone infection: Redefining “biofilm,”
Volume 9 Issue 3 (2023) 76 https://doi.org/10.18063/ijb.683

