Coupling Additive Manufacturing with Hot Melt Extrusion Technologies to Validate a Ventilator-Associated Pneumonia Mouse Model
Bahaa Shaqour,
Juliana Aizawa,
Clara Guarch-Pérez,
Żaneta Górecka,
Lars Christophersen,
Wim Martinet,
Emilia Choińska,
Martijn Riool,
Bart Verleije,
Koen Beyers,
Claus Moser,
Wojciech Święszkowski,
Sebastian A. J. Zaat,
Paul Cos
Affiliations
Bahaa Shaqour
Laboratory for Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1 S.7, 2610 Wilrijk, Belgium
Juliana Aizawa
Laboratory for Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1 S.7, 2610 Wilrijk, Belgium
Clara Guarch-Pérez
Department of Medical Microbiology and Infection Prevention, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
Żaneta Górecka
Faculty of Materials Sciences and Engineering, Warsaw University of Technology, Woloska 141, 02-507 Warsaw, Poland
Lars Christophersen
Department for Clinical Microbiology, Rigshospitalet, Henrik Harpestrengsvej 4A, Afsnit 93.01, 2100 Copenhagen, Denmark
Wim Martinet
Laboratory of Physiopharmacology, University of Antwerp, Universiteitsplein 1 T.2, 2610 Wilrijk, Belgium
Emilia Choińska
Faculty of Materials Sciences and Engineering, Warsaw University of Technology, Woloska 141, 02-507 Warsaw, Poland
Martijn Riool
Department of Medical Microbiology and Infection Prevention, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
Department for Clinical Microbiology, Rigshospitalet, Henrik Harpestrengsvej 4A, Afsnit 93.01, 2100 Copenhagen, Denmark
Wojciech Święszkowski
Faculty of Materials Sciences and Engineering, Warsaw University of Technology, Woloska 141, 02-507 Warsaw, Poland
Sebastian A. J. Zaat
Department of Medical Microbiology and Infection Prevention, Amsterdam Institute for Infection and Immunity, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
Paul Cos
Laboratory for Microbiology, Parasitology and Hygiene (LMPH), Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1 S.7, 2610 Wilrijk, Belgium
Additive manufacturing is widely used to produce highly complex structures. Moreover, this technology has proven its superiority in producing tools which can be used in different applications. We designed and produced an extrusion nozzle that allowed us to hot melt extrude drug-loaded tubes. The tubes were an essential part of a new mouse ventilator-associated pneumonia (VAP) model. Ciprofloxacin (CPX) was selected for its expected activity against the pathogen Staphylococcus aureus and ease of incorporation into thermoplastic polyurethane (TPU). TPU was selected as the carrier polymer for its biocompatibility and use in a variety of medical devices such as tubing and catheters. The effect of loading CPX within the TPU polymeric matrix and the physicochemical properties of the produced tubes were investigated. CPX showed good thermal stability and in vitro activity in preventing S. aureus biofilm formation after loading within the tube’s polymeric matrix. Moreover, the produced tubes showed anti-infective efficacy in vivo. The produced tubes, which were extruded via our novel nozzle, were vital for the validation of our mouse VAP model. This model can be adopted to investigate other antibacterial and antibiofilm compounds incorporated in polymeric tubes using hot melt extrusion.
