PMID- 37273978 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230606 IS - 2424-8002 (Electronic) IS - 2424-7723 (Print) IS - 2424-8002 (Linking) VI - 9 IP - 3 DP - 2023 TI - 3D-printed dual drug delivery nanoparticle- loaded hydrogels to combat antibiotic-resistant bacteria. PG - 683 LID - 10.18063/ijb.683 [doi] LID - 683 AB - 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 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 21 days. Low molecular weight PLGA NPs exhibited the fastest release of Rif and Van within the first 7 days and were selected for antimicrobial evaluation. Four different GelMA-based 3D-printed samples were successfully produced, carrying non-loaded NPs, Rif-NPs, Van-NPs, or alternating layers of Rif-NPs and Van-NP. The exposition of S. aureus against increased concentrations of Rif or Van produced new resistant strains to Rif (Rif(R)) or Van (Van(R)). The GelMA hydrogel co-delivering Rif and Van eradicated S. aureus RN4220 Rif(R) and RN4220 Van(R) strains. S. aureus RN4220 and S. aureus AMC 201 colonies developed resistance to Rif after contact with the GelMA hydrogel containing only Rif-NPs which appeared to be due to known mutations in the rpoB gene. In conclusion, 3D-printed GelMA hydrogel loaded with PLGA Rif-Van-NPs drug delivery system show promising in vitro results to prevent implant-associated infections caused by antimicrobial-resistant bacteria. CI - Copyright: (c) 2023 Martinez-Perez D, Guarch-Perez C, Purbayanto MAK, et al. FAU - Martinez-Perez, David AU - Martinez-Perez D AD - Faculty of Materials Science and Engineering, Warsaw University of Technology, Woloska 141, 02-507, Warsaw, Poland. FAU - Guarch-Perez, Clara AU - Guarch-Perez C AD - 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. FAU - Purbayanto, Muhammad Abiyyu Kenichi AU - Purbayanto MAK AD - Faculty of Materials Science and Engineering, Warsaw University of Technology, Woloska 141, 02-507, Warsaw, Poland. FAU - Choinska, Emilia AU - Choinska E AD - Faculty of Materials Science and Engineering, Warsaw University of Technology, Woloska 141, 02-507, Warsaw, Poland. FAU - Riool, Martijn AU - Riool M AD - 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. FAU - Zaat, Sebastian A J AU - Zaat SAJ AD - 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. FAU - Wojciech, Swieszkowski AU - Wojciech S AD - Faculty of Materials Science and Engineering, Warsaw University of Technology, Woloska 141, 02-507, Warsaw, Poland. LA - eng PT - Journal Article DEP - 20230213 PL - Singapore TA - Int J Bioprint JT - International journal of bioprinting JID - 101709763 PMC - PMC10236340 OTO - NOTNLM OT - 3D printing OT - Antibiotic resistance OT - Controlled drug delivery OT - Gelatin methacrylate OT - Nanoparticles OT - Staphylococcus aureus COIS- The authors declare no conflicts of interest. EDAT- 2023/06/05 13:04 MHDA- 2023/06/05 13:05 PMCR- 2023/02/13 CRDT- 2023/06/05 11:55 PHST- 2022/10/04 00:00 [received] PHST- 2022/11/08 00:00 [accepted] PHST- 2023/06/05 13:05 [medline] PHST- 2023/06/05 13:04 [pubmed] PHST- 2023/06/05 11:55 [entrez] PHST- 2023/02/13 00:00 [pmc-release] AID - IJB-9-3-683 [pii] AID - 10.18063/ijb.683 [doi] PST - epublish SO - Int J Bioprint. 2023 Feb 13;9(3):683. doi: 10.18063/ijb.683. eCollection 2023.