Abstract

Chronic infection as a result of bacterial biofilm formation on implanted medical devices is a major global healthcare problem requiring new biocompatible, biofilm-resistant materials. Here we demonstrate how bespoke devices can be manufactured through ink-jet-based 3D printing using bacterial biofilm inhibiting formulations without the need for eluting antibiotics or coatings. Candidate monomers were formulated and their processability and reliability demonstrated. Formulations for in vivo evaluation of the 3D printed structures were selected on the basis of their in vitro bacterial biofilm inhibitory properties and lack of mammalian cell cytotoxicity. In vivo in a mouse implant infection model, Pseudomonas aeruginosa biofilm formation on poly-TCDMDA was reduced by ∼99% when compared with medical grade silicone. Whole mouse bioluminescence imaging and tissue immunohistochemistry revealed the ability of the printed device to modulate host immune responses as well as preventing biofilm formation on the device and infection of the surrounding tissues. Since 3D printing can be used to manufacture devices for both prototyping and clinical use, the versatility of ink-jet based 3D-printing to create personalised functional medical devices is demonstrated by the biofilm resistance of both a finger joint prosthetic and a prostatic stent printed in poly-TCDMDA towards P. aeruginosa and Staphylococcus aureus.

Highlights

  • Infections associated with implanted medical devices such as cath­ eters, stents and prosthetic joint replacements are responsible for sig­ nificant patient morbidity and mortality [1,2]

  • Biomaterials 281 (2022) 121350 and a prostatic stent [34,35,36,37] to exemplify the range and complexity of structures printable with this technique. We demonstrate their resis­ tance to biofilm formation such that our study introduces non-fouling biomaterials for such devices, and exploits an advanced manufacturing method for medical devices that are adaptable to indi­ vidual patient needs

  • Photoreactive monomer candidates were selected based on screening for resistance to bacterial biofilm formation and assessed for their capacity for consistent and reliable deposition from an ink-jet print head

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Summary

Introduction

Infections associated with implanted medical devices such as cath­ eters, stents and prosthetic joint replacements are responsible for sig­ nificant patient morbidity and mortality [1,2] They are a major complication of orthopaedic and trauma surgery and impose a signifi­ cant economic burden on healthcare services worldwide. Such infections are generally chronic and caused by bacterial pathogens such as Pseu­ domonas aeruginosa and Staphylococcus aureus forming biofilms on implant surfaces within which bacterial cells are localized in a self-generated matrix consisting of polysaccharides, proteins, lipids and extracellular DNA. We demonstrate their resis­ tance to biofilm formation such that our study introduces non-fouling biomaterials for such devices, and exploits an advanced manufacturing method for medical devices that are adaptable to indi­ vidual patient needs

Results
Mechanical properties
Bacterial biofilm formation on polymer cuboid arrays
Mammalian cell Cytotoxicity and attachment
Spectroscopic assessment of curability
Exemplars of ink-jet based 3D printed biofilm resistant devices
Conclusions
Ink preparation
Sample printing
Polymer mechanical and chemical properties
Mammalian cell cytotoxicity
Bacterial biofilm formation
Declaration of competing interest
Full Text
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