Page 72 - IJB-9-3

International Journal of Bioprinting

RESEARCH ARTICLE
3D-printed dual drug delivery nanoparticle-

loaded hydrogels to combat antibiotic-resistant
bacteria

David Martínez-Pérez , Clara Guarch-Pérez ,
2†
1†
Muhammad Abiyyu Kenichi Purbayanto , Emilia Choińska , Martijn Riool ,
1
2
1
Sebastian A. J. Zaat , Wojciech Święszkowski *
1
2
1 Faculty of Materials Science and Engineering, Warsaw University of Technology, Wołoska 141,
02-507, Warsaw, Poland
2 Department of Medical Microbiology and Infection Prevention, Amsterdam Institute for Infection
and Immunity, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam,
the Netherlands
Abstract

Implant-associated infections are not easy to diagnose and very difficult to treat, due
to the ability of major pathogens, such as Staphylococcus aureus, to develop biofilms
and escape the immune response and antibiotic treatment. We, therefore, aimed to
develop a 3D-printed dual rifampicin (Rif)- and vancomycin (Van)-loaded polylactic-
co-glycolic acid (PLGA) nanoparticles (NPs) delivery system based on hydrogels made
† These authors contributed equally
to this work. of gelatin methacrylate (GelMA). The release of Rif and Van from NPs manufactured
from different PLGA molecular weights was studied in phosphate-buffered saline for
*Corresponding author: 21 days. Low molecular weight PLGA NPs exhibited the fastest release of Rif and Van
Wojciech Święszkowski
(wojciech.swieszkowski@pw.edu.pl) within the first 7 days and were selected for antimicrobial evaluation. Four different
GelMA-based 3D-printed samples were successfully produced, carrying non-loaded
Citation: Martínez-Pérez D,
Guarch-Pérez C, Purbayanto NPs, Rif-NPs, Van-NPs, or alternating layers of Rif-NPs and Van-NP. The exposition of S.
MAK, et al., 2023, 3D-printed dual aureus against increased concentrations of Rif or Van produced new resistant strains
drug delivery nanoparticle-loaded to Rif (Rif ) or Van (Van ). The GelMA hydrogel co-delivering Rif and Van eradicated
R
R
hydrogels to combat antibiotic-
R
R
resistant bacteria. Int J Bioprint, S. aureus RN4220 Rif and RN4220 Van strains. S. aureus RN4220 and S. aureus AMC
9(3): 683. 201 colonies developed resistance to Rif after contact with the GelMA hydrogel
https://doi.org/10.18063/ijb.683 containing only Rif-NPs which appeared to be due to known mutations in the rpoB
Received: October 04, 2022 gene. In conclusion, 3D-printed GelMA hydrogel loaded with PLGA Rif-Van-NPs
Accepted: November 08, 2022 drug delivery system show promising in vitro results to prevent implant-associated
Published Online: February 13,
2023 infections caused by antimicrobial-resistant bacteria.
Copyright: © 2023 Author(s).
This is an Open Access article Keywords: 3D printing; Antibiotic resistance; Staphylococcus aureus; Controlled
distributed under the terms of the drug delivery; Gelatin methacrylate; Nanoparticles
Creative Commons Attribution
License, permitting distribution,
and reproduction in any medium,
provided the original work is
properly cited.
1. Introduction
Publisher’s Note: Whioce
Publishing remains neutral with Implant-associated infection is a devastating healthcare complication worldwide. The
regard to jurisdictional claims in infection rates in patients with total arthroplasties for the hip and knee are 0.5%–1%
published maps and institutional
affiliations. and 1%–4%, respectively. Infection rates from closed fractures with fracture fixation

Volume 9 Issue 3 (2023) 64 https://doi.org/10.18063/ijb.683