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 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.

A Niclosamide-releasing hot-melt extruded catheter prevents Staphylococcus aureus experimental biomaterial-associated infection

“…T onset for 2, 5 and 10% NIC loaded TPU were 315 °C, 313 °C and 311 °C, respectively. Such increase in T onset was also reported when TPU was loaded with ciprofloxacin 29 or tetracycline hydrochloride 40 , which indicates that, like NIC, the presence of these compounds improved the thermal stability of the polymer.…”

“…TPU was loaded with NIC at 2, 5 and 10% ( w/w ) using the solvent casting approach adopted from the work of Shaqour et al . 29 , as shown in Fig. 1 A.…”

“…The extruded fibers were cut into 4 cm segments and used to evaluate the effect of NIC loading on the mechanical properties of the TPU, while the extruded catheters segments (0.5 and 1 cm length) were used for material characterization and for microbiological characterization. Catheter segments for microbiological testing were further sterilized by incubation in ethanol 70% for 1 min followed by air-drying for 30 s 29 .…”

“…Catheters from each group were imaged and then analyzed using ImageJ software version 1.52a 31 ( https://imagej.nih.gov/ij/ ) by calculating the equivalent diameter (Eq. 1 ) of the measured area for the inner and outer circles for each catheter ( n = 6 for each group) 29 . …”

Maternal Separation Induced Visceral Hypersensitivity Evaluated via Novel and Small Size Distention Balloon in Post-weaning Mice

“…Moloney et al (2012) developed a mouse model of MS stress-induced visceral hyperalgesia as measured by CRD (Moloney et al, 2012); from then on, MS of mice model were extensively conducted to study the mechanism underlying the pathogenesis of IBS, such as intestinal dysbiosis, intestinal dysfunction, intestinal permeability alteration, and IBS-like anxiety and depression behaviors (De Palma et al, 2015;Li et al, 2017;Riba et al, 2017;Rincel et al, 2019;Zhou et al, 2020). Indeed, compared with the rat model, the mouse model of MS had the advantages of its small size, relatively high reproductivity, inexpensive, and can be genetically manipulated (Kong et al, 2013;Shaqour et al, 2021). Because early postnatal life is a critical period during which both brain and gut undergo important maturation (Borre et al, 2014;Sharon et al, 2016), this period constitutes a critical window of sensitivity to stress (Rincel and Darnaudéry, 2020).…”