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

doi:10.3390/pharmaceutics13060772

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

^*Corresponding author for this work

University of Antwerp
An-Najah National University
University of Amsterdam
Warsaw University of Technology
University of Copenhagen
Voxdale bv, Bijkhoevelaan 32, 2110, Wijnegem, Belgium

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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 appli-cations. 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.

Original language	English
Article number	772
Journal	Pharmaceutics
Volume	13
Issue number	6
DOIs	https://doi.org/10.3390/pharmaceutics13060772
Publication status	Published - 1 Jun 2021

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being
SDG 9 Industry, Innovation, and Infrastructure

Keywords

Additive manufacturing
Anti-infective
Antibiofilm
Biomaterials
Ciprofloxacin
Endotracheal tubes
Extrusion die
Extrusion nozzle
Hot melt extrusion
Medical devices
Staphylococcus aureus
Ventilator-associated pneumonia

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Shaqour, B., Aizawa, J., Guarch-Pérez, C., Górecka, Ż., Christophersen, L., Martinet, W., Choińska, E., Riool, M., Verleije, B., Beyers, K., Moser, C., Święszkowski, W., Zaat, S. A. J., & Cos, P. (2021). Coupling additive manufacturing with hot melt extrusion technologies to validate a ventilator-associated pneumonia mouse model. Pharmaceutics, 13(6), Article 772. https://doi.org/10.3390/pharmaceutics13060772

@article{001a71afc26a46b399d4cec1a6c4da8a,

title = "Coupling additive manufacturing with hot melt extrusion technologies to validate a ventilator-associated pneumonia mouse model",

abstract = "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 appli-cations. 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{\textquoteright}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.",

keywords = "Additive manufacturing, Anti-infective, Antibiofilm, Biomaterials, Ciprofloxacin, Endotracheal tubes, Extrusion die, Extrusion nozzle, Hot melt extrusion, Medical devices, Staphylococcus aureus, Ventilator-associated pneumonia",

author = "Bahaa Shaqour and Juliana Aizawa and Clara Guarch-P{\'e}rez and {\.Z}aneta G{\'o}recka and Lars Christophersen and Wim Martinet and Emilia Choi{\'n}ska and Martijn Riool and Bart Verleije and Koen Beyers and Claus Moser and Wojciech {\'S}wi{\c e}szkowski and Zaat, \{Sebastian A. J.\} and Paul Cos",

note = "Funding Information: Conflicts of Interest: The authors declare no conflict of interest. Voxdale has been funded by European Union{\textquoteright}s Horizon 2020 research and innovation programme under the Marie Sk{\l}odowska-Curie grant agreement No. 722467 to support activities performed by B.S. in designing and producing the nozzle. Voxdale has accepted publishing this submitted manuscript. Funding Information: Funding: This work was funded by the research project PRINTAID, within the EU Framework Programme for Research and Innovation Horizon 2020—Marie Sklodowska-Curie Innovative Training Networks under grant agreement No. 722467. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = jun,

day = "1",

doi = "10.3390/pharmaceutics13060772",

language = "English",

volume = "13",

journal = "Pharmaceutics",

issn = "1999-4923",

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Shaqour, B, Aizawa, J, Guarch-Pérez, C, Górecka, Ż, Christophersen, L, Martinet, W, Choińska, E, Riool, M, Verleije, B, Beyers, K, Moser, C, Święszkowski, W, Zaat, SAJ & Cos, P 2021, 'Coupling additive manufacturing with hot melt extrusion technologies to validate a ventilator-associated pneumonia mouse model', Pharmaceutics, vol. 13, no. 6, 772. https://doi.org/10.3390/pharmaceutics13060772

TY - JOUR

T1 - Coupling additive manufacturing with hot melt extrusion technologies to validate a ventilator-associated pneumonia mouse model

AU - Shaqour, Bahaa

AU - Aizawa, Juliana

AU - Guarch-Pérez, Clara

AU - Górecka, Żaneta

AU - Christophersen, Lars

AU - Martinet, Wim

AU - Choińska, Emilia

AU - Riool, Martijn

AU - Verleije, Bart

AU - Beyers, Koen

AU - Moser, Claus

AU - Święszkowski, Wojciech

AU - Zaat, Sebastian A. J.

AU - Cos, Paul

N1 - Funding Information: Conflicts of Interest: The authors declare no conflict of interest. Voxdale has been funded by European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 722467 to support activities performed by B.S. in designing and producing the nozzle. Voxdale has accepted publishing this submitted manuscript. Funding Information: Funding: This work was funded by the research project PRINTAID, within the EU Framework Programme for Research and Innovation Horizon 2020—Marie Sklodowska-Curie Innovative Training Networks under grant agreement No. 722467. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/6/1

Y1 - 2021/6/1

N2 - 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 appli-cations. 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.

AB - 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 appli-cations. 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.

KW - Additive manufacturing

KW - Anti-infective

KW - Antibiofilm

KW - Biomaterials

KW - Ciprofloxacin

KW - Endotracheal tubes

KW - Extrusion die

KW - Extrusion nozzle

KW - Hot melt extrusion

KW - Medical devices

KW - Staphylococcus aureus

KW - Ventilator-associated pneumonia

UR - https://www.scopus.com/pages/publications/85107304891

U2 - 10.3390/pharmaceutics13060772

DO - 10.3390/pharmaceutics13060772

M3 - Article

C2 - 34064276

SN - 1999-4923

VL - 13

JO - Pharmaceutics

JF - Pharmaceutics

IS - 6

M1 - 772

ER -

Coupling additive manufacturing with hot melt extrusion technologies to validate a ventilator-associated pneumonia mouse model

Abstract

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Keywords

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