scholarly journals It takes two for chronic wounds to heal: dispersing bacterial biofilm and modulating inflammation with dual action plasma coatings

RSC Advances ◽  
2020 ◽  
Vol 10 (13) ◽  
pp. 7368-7376 ◽  
Author(s):  
Thomas Danny Michl ◽  
Dung Thuy Thi Tran ◽  
Hannah Frederike Kuckling ◽  
Aigerim Zhalgasbaikyzy ◽  
Barbora Ivanovská ◽  
...  
Keyword(s):  
Chronic Wounds ◽  
Nitroxide Radical ◽  
Bacterial Biofilm ◽  
Thin Coatings ◽  
The Future ◽  
Dual Action ◽  
Infection And Inflammation ◽  
Plasma Coatings ◽  
Stable Nitroxide

We plasma polymerized the stable nitroxide radical TEMPO into thin coatings and exploited the coatings' unique qualities in targeting both infection and inflammation simultaneously; demonstrating a novel alternative as to how chronic wounds could be treated in the future.

scholarly journals Vesicle-associatedPseudomonas aeruginosaleucine aminopeptidase modulates bacterial biofilms grown on host cellular substrates

2019 ◽  
Author(s):  
Caitlin N. Esoda ◽  
Meta J. Kuehn
Keyword(s):  
Biofilm Formation ◽  
Chronic Wounds ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Bacterial Biofilm ◽  
Lung Epithelial ◽  
Coculture Model ◽  
Chronic Colonization ◽  
Bacterial Outer Membrane ◽  
Future Work

AbstractPseudomonas aeruginosa, known as one of the leading causes of morbidity and mortality in cystic fibrosis (CF) patients, secretes a variety of virulence-associated proteases. These enzymes have been shown to contribute significantly toP. aeruginosapathogenesis and biofilm formation in the chronic colonization of CF patient lungs, as well as playing a role in infections of the cornea, burn wounds and chronic wounds. Our lab has previously characterized a secretedP. aeruginosapeptidase, PaAP, that is highly expressed in chronic CF isolates. This leucine aminopeptidase is not only secreted solubly, it also associates with bacterial outer membrane vesicles (OMVs), structures known for their contribution to virulence mechanisms in a variety of Gram-negative species and one of the major components of the biofilm matrix. With this in mind, we hypothesized that PaAP may play a role inP. aeruginosabiofilm formation. Using a lung epithelial cell/bacterial biofilm coculture model, we show that PaAP deletion in a clinicalP. aeruginosabackground leads to increased early biofilm formation. We additionally found that only native vesicle-bound PaAP, as opposed to its soluble forms, could reconstitute the original PaAP-mediated inhibition phenotype, and that the PaAP-containing vesicles could disperse preformed biofilm microcolonies ofKlebsiella pneumoniae, another lung pathogen. These data provide the basis for future work into the mechanism behind PaAP-OMV mediated bacterial microcolony dispersal and the application of these findings to clinical anti-biofilm research.

A dual-action peptide-containing hydrogel targets wound infection and inflammation

2020 ◽  
Vol 12 (524) ◽  
pp. eaax6601 ◽  
Author(s):  
Manoj Puthia ◽  
Marta Butrym ◽  
Jitka Petrlova ◽  
Ann-Charlotte Strömdahl ◽  
Madelene Å. Andersson ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Nuclear Factor Κb ◽  
Reporter Mice ◽  
Dual Action ◽  
Infection And Inflammation ◽  
Molecular Patterns

There is a clinical need for improved wound treatments that prevent both infection and excessive inflammation. TCP-25, a thrombin-derived peptide, is antibacterial and scavenges pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide, thereby preventing CD14 interaction and Toll-like receptor dimerization, leading to reduced downstream immune activation. Here, we describe the development of a hydrogel formulation that was functionalized with TCP-25 to target bacteria and associated PAMP-induced inflammation. In vitro studies determined the polymer prerequisites for such TCP-25–mediated dual action, favoring the use of noncharged hydrophilic hydrogels, which enabled peptide conformational changes and LPS binding. The TCP-25–functionalized hydrogels killed Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa bacteria in vitro, as well as in experimental mouse models of subcutaneous infection. The TCP-25 hydrogel also mediated reduction of LPS-induced local inflammatory responses, as demonstrated by analysis of local cytokine production and in vivo bioimaging using nuclear factor κB (NF-κB) reporter mice. In porcine partial thickness wound models, TCP-25 prevented infection with S. aureus and reduced concentrations of proinflammatory cytokines. Proteolytic fragmentation of TCP-25 in vitro yielded a series of bioactive TCP fragments that were identical or similar to those present in wounds in vivo. Together, the results demonstrate the therapeutic potential of TCP-25 hydrogel, a wound treatment based on the body’s peptide defense, for prevention of both bacterial infection and the accompanying inflammation.

scholarly journals To be a radical or not to be one? The fate of the stable nitroxide radical TEMPO [(2,2,6,6-Tetramethylpiperidin-1-yl)oxyl] undergoing plasma polymerization into thin-film coatings

2020 ◽  
Vol 15 (3) ◽  
pp. 031015 ◽  
Author(s):  
Thomas Danny Michl ◽  
Dung Thuy Thi Tran ◽  
Kilian Böttle ◽  
Hannah Frederike Kuckling ◽  
Aigerim Zhalgasbaikyzy ◽  
...  
Keyword(s):  
Thin Film ◽  
Plasma Polymerization ◽  
Nitroxide Radical ◽  
Film Coatings ◽  
Thin Film Coatings ◽  
Stable Nitroxide

Addition of Stable Nitroxide Radical to Stable Divalent Compounds of Heavier Group 14 Elements

2003 ◽  
Vol 125 (31) ◽  
pp. 9300-9301 ◽  
Author(s):  
Takeaki Iwamoto ◽  
Hidenori Masuda ◽  
Shintaro Ishida ◽  
Chizuko Kabuto ◽  
Mitsuo Kira
Keyword(s):  
Nitroxide Radical ◽  
Group 14 ◽  
Group 14 Elements ◽  
Stable Nitroxide

scholarly journals New Adapted In Vitro Technology to Evaluate Biofilm Formation and Antibiotic Activity Using Live Imaging under Flow Conditions

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1746
Author(s):  
Cassandra Pouget ◽  
Catherine Dunyach-Remy ◽  
Alix Pantel ◽  
Sophie Schuldiner ◽  
Albert Sotto ◽  
...  
Keyword(s):  
Biofilm Formation ◽  
Cell Imaging ◽  
Chronic Wounds ◽  
Chronic Wound ◽  
Live Imaging ◽  
Bacterial Biofilm ◽  
Flow Conditions ◽  
Promising Tool ◽  
Reference Strains

The polymicrobial nature of biofilms and bacterial interactions inside chronic wounds are keys for the understanding of bacterial cooperation. The aim of this present study was to develop a technique to study and visualize biofilm in live imaging under flow conditions (Bioflux™ 200, Fluxion Biosciences). The BiofluxTM system was adapted using an in vitro chronic wound-like medium (CWM) that mimics the environment encountered in ulcers. Two reference strains of Staphylococcus aureus (Newman) and Pseudomonas aeruginosa (PAO1) were injected in the BiofluxTM during 24 h to 72 h in mono and coculture (ratio 1:1, bacteria added simultaneously) in the CWM vs. a control medium (BHI). The quantification of biofilm formation at each time was evaluated by inverted microscopy. After 72 h, different antibiotics (ceftazidime, imipenem, linezolid, oxacillin and vancomycin) at 1x MIC, 10x MIC and 100x MIC were administrated to the system after an automatic increase of the flow that mimicked a debridement of the wound surface. Biofilm studies highlighted that the two species, alone or associated, constituted a faster and thicker biofilm in the CWM compared to the BHI medium. The effect of antibiotics on mature or “debrided” biofilm indicated that some of the most clinically used antibiotic such as vancomycin or imipenem were not able to disrupt and reduce the biofilm biomass. The use of a life cell imaging with an in vitro CWM represents a promising tool to study bacterial biofilm and investigate microbial cooperation in a chronic wound context.

Crystal and Molecular Structure of 3-(N-Methoxy-N-methylcarbamoyl)- 2,2,5,5-tetramethyl-1-oxy-pyrroline

2010 ◽  
Vol 65 (4) ◽  
pp. 475-478
Author(s):  
Guido D. Frey ◽  
Eberhardt Herdtweck
Keyword(s):  
Molecular Structure ◽  
Crystal Structure ◽  
Solid State ◽  
Hydrogen Bonds ◽  
Crystal And Molecular Structure ◽  
Layer Structure ◽  
Nitroxide Radical ◽  
Orthorhombic Space Group ◽  
X Ray ◽  
Stable Nitroxide

The crystal structure of the stable nitroxide radical 3-(N-methoxy-N-methylcarbamoyl)-2,2,5,5- tetramethyl-1-oxy-pyrroline was determined from single-crystal X-ray data: orthorhombic, space group Pbca (no. 61), a = 9.0213(1), b = 12.8625(1), c = 21.2406(2) Å, V = 2464.68(4) Å3 and Z = 8. The adjacent molecules assemble to a supramolecular layer structure in the solid state, linked by two intermolecular C-H...O hydrogen bonds.

scholarly journals A stable nitroxide radical effectively decreases mucosal damage in experimental colitis.

Gut ◽  
1995 ◽  
Vol 37 (3) ◽  
pp. 386-393 ◽  
Author(s):  
F Karmeli ◽  
R Eliakim ◽  
E Okon ◽  
A Samuni ◽  
D Rachmilewitz
Keyword(s):  
Nitroxide Radical ◽  
Experimental Colitis ◽  
Mucosal Damage ◽  
Stable Nitroxide

The structure and absolute stereochemistry of caryophyllene “iodo-nitrosite”: a stable nitroxide radical

1967 ◽  
Vol 0 (18) ◽  
pp. 942-943 ◽  
Author(s):  
D. M. Hawley ◽  
J. S. Roberts ◽  
G. Ferguson ◽  
A. L. Porte
Keyword(s):  
Nitroxide Radical ◽  
Absolute Stereochemistry ◽  
Stable Nitroxide

Quenching of the Perylene Fluorophore by Stable Nitroxide Radical-Containing Macromolecules

2014 ◽  
Vol 118 (43) ◽  
pp. 12541-12548 ◽  
Author(s):  
Barbara K. Hughes ◽  
Wade A. Braunecker ◽  
Andrew J. Ferguson ◽  
Travis W. Kemper ◽  
Ross E. Larsen ◽  
...  
Keyword(s):  
Nitroxide Radical ◽  
Stable Nitroxide
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