Development of dual anti-biofilm and anti-bacterial medical devices

Burroughs, Laurence; Ashraf, Waheed; Singh, Sonali; Martı́nez-Pomares, Luisa; Bayston, Roger; Hook, Andrew L.

doi:10.1039/d0bm00709a

Cited by 24 publications

(13 citation statements)

References 35 publications

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“…We selected a series of weakly amphiphilic monomers from a library of 16 acrylates and methacrylates (Figure SI1, 1-16) that had previously been shown to resist biofilm formation when polymerized [ [27] , [28] , [29] , 36 ], and have also been shown to permit the permeation of antimicrobials for the creation of dual-functional anti-biofilm and anti-microbial coatings [ 37 ]. Since PEG based materials have been widely studied for their ability to prevent fouling by both blood proteins and host cells [ 22 ], monomers 1–16 were each combinatorially mixed with acrylate glycol monomers of varying chain lengths ( Figure SI1, A-D ) at volume ratios of 100:0 (homopolymers), 75:25, 50:50, 25:75 and 0:100 and copolymerized.…”

Section: Resultsmentioning

confidence: 99%

Discovery of hemocompatible bacterial biofilm-resistant copolymers

et al. 2020

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Blood-contacting medical devices play an important role within healthcare and are required to be biocompatible, hemocompatible and resistant to microbial colonization. Here we describe a high throughput screen for copolymers with these specific properties. A series of weakly amphiphilic monomers are combinatorially polymerized with acrylate glycol monomers of varying chain lengths to create a library of 645 multi-functional candidate materials containing multiple chemical moieties that impart anti-biofilm, hemo- and immuno-compatible properties. These materials are screened in over 15,000 individual biological assays, targeting two bacterial species, one Gram negative ( Pseudomonas aeruginosa ) and one Gram positive ( Staphylococcus aureus ) commonly associated with central venous catheter infections, using 5 different measures of hemocompatibility and 6 measures of immunocompatibililty. Selected copolymers reduce platelet activation, platelet loss and leukocyte activation compared with the standard comparator PTFE as well as reducing bacterial biofilm formation in vitro by more than 82% compared with silicone. Poly(isobornyl acrylate-co-triethylene glycol methacrylate) (75:25) is identified as the optimal material across all these measures reducing P. aeruginosa biofilm formation by up to 86% in vivo in a murine foreign body infection model compared with uncoated silicone.

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Section: Resultsmentioning

confidence: 99%

Discovery of hemocompatible bacterial biofilm-resistant copolymers

et al. 2020

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“…Given that rifampicin specifically targets the bacterial DNA-dependent RNA polymerase, we confirmed that, at the concentration tested, this drug does not provoke any side effect on fibroblasts in terms of cell viability. However, cytotoxicity of chlorhexidine to eukaryotic cells is well known [ 33 , 40 ]. It was demonstrated that this antiseptic could reduce the growth pattern of cultured cells, as well as provoke morphological modifications on fibroblasts [ 41 ], which corroborates our cell viability results.…”

Section: Discussionmentioning

confidence: 99%

Development of Biocomposite Polymeric Systems Loaded with Antibacterial Nanoparticles for the Coating of Polypropylene Biomaterials

et al. 2020

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The development of a biocomposite polymeric system for the antibacterial coating of polypropylene mesh materials for hernia repair is reported. Coatings were constituted by a film of chitosan containing randomly dispersed poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles loaded with chlorhexidine or rifampicin. The chlorhexidine-loaded system exhibited a burst release during the first day reaching the release of the loaded drug in three or four days, whereas rifampicin was gradually released for at least 11 days. Both antibacterial coated meshes were highly active against Staphylococcus aureus and Staphylococcus epidermidis (106 CFU/mL), displaying zones of inhibition that lasted for 7 days (chlorhexidine) or 14 days (rifampicin). Apparently, both systems inhibited bacterial growth in the surrounding environment, as well as avoided bacterial adhesion to the mesh surface. These polymeric coatings loaded with biodegradable nanoparticles containing antimicrobials effectively precluded bacterial colonization of the biomaterial. Both biocomposites showed adequate performance and thus could have potential application in the design of antimicrobial coatings for the prophylactic coating of polypropylene materials for hernia repair.

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“…In another postfabrication strategy, drugs are impregnated into the polymeric device bulk with assistance of an organic solvent that is able to dissolve the drug and swell the polymer. 7,8 The downside of this approach is that it requires excessive solvents and drugs, and the swelling and drying processes are time-consuming. In contrast to these postfabrication methods, drugs may also be first mixed with the polymers or polymer precursors.…”

Section: ■ Introductionmentioning

confidence: 99%

“…A common postdevice modification method is the creation of a drug-embedded coating on the surface of medical devices. , However, a thin coating layer can only hold limited amounts of drugs and the coating may be delaminated during use if the adhesion is not well optimized. In another postfabrication strategy, drugs are impregnated into the polymeric device bulk with assistance of an organic solvent that is able to dissolve the drug and swell the polymer. , The downside of this approach is that it requires excessive solvents and drugs, and the swelling and drying processes are time-consuming. In contrast to these postfabrication methods, drugs may also be first mixed with the polymers or polymer precursors.…”

Section: Introductionmentioning

confidence: 99%

3D Printing of Antibacterial Polymer Devices Based on Nitric Oxide Release from Embedded S-Nitrosothiol Crystals

Yang

Ehrhardt

et al. 2021

ACS Appl. Bio Mater.

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Controlled release of drugs from medical implants is an effective approach to reducing foreign body reactions and infections. We report here on a one-step 3D printing strategy to create drug-eluting polymer devices with a drug-loaded bulk and a drug-free coating. The spontaneously formed drug-free coating dramatically reduces the surface roughness of the implantable devices and serves as a protective layer to suppress the burst release of drugs. A high viscosity liquid silicone that can be extruded based on its shear-thinning property and quickly vulcanize upon exposure to ambient moisture is used as the ink for 3D printing. S-Nitrosothiol type nitric oxide (NO) donors in their crystalline forms are selected as model drugs because of the potent antimicrobial, antithrombotic, and anti-inflammatory properties of NO. Direct ink writing of the homogenized polymer-drug mixtures generates rough and ill-defined device surfaces because of the exposed S-nitrosothiol microparticles. When a low-viscosity silicone (polydimethylsiloxane) is added into the ink, this silicone diffuses outward upon deposition to form a drug-free outermost layer without compromising the integrity of the printed structures. S-Nitrosoglutathione (GSNO) or S-nitroso-N-acetylpenicillamine (SNAP) embedded in the printed silicone matrix releases NO under physiological conditions from days to about one month. The microsized drug crystals are well-preserved in the ink preparation and printing processes, which is one reason for the sustained NO release. Biofilm and cytotoxicity experiments confirmed the antibacterial property and safety of the printed NO-releasing devices. This additive manufacturing platform does not require dissolution of drugs and involves no thermal or UV processes and, therefore, offers unique opportunities to produce drug-eluting silicone devices in a customized manner.

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Development of dual anti-biofilm and anti-bacterial medical devices

Abstract: Silicone catheters impregnated with antibiotics and coated with an anti-attachment polyacrylate produce a device with dual anti-biofilm and anti-bacterial properties.

Cited by 24 publications

References 35 publications

Discovery of hemocompatible bacterial biofilm-resistant copolymers

Discovery of hemocompatible bacterial biofilm-resistant copolymers

Development of Biocomposite Polymeric Systems Loaded with Antibacterial Nanoparticles for the Coating of Polypropylene Biomaterials

3D Printing of Antibacterial Polymer Devices Based on Nitric Oxide Release from Embedded S-Nitrosothiol Crystals

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