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Antibiofilm and Immune Response of Engineered Bioactive Nanoparticles for Endodontic Disinfection.

ABSTRACT: The biological aim of root canal treatment is to facilitate periapical tissue healing following endodontic therapy. This study aimed to develop an organotypic infected root canal model to understand the interaction of bacterial biofilm with macrophages and study the therapeutic effect of engineered bioactive chitosan nanoparticles (CSnp) on macrophages. Ex-vivo experiments were conducted in two phases; Phase-1: Enterococcus faecalis biofilms (two and six weeks old) developed in organotypic root canal model were used to characterize residual biofilm after conventional chemical treatment alone and combined with CSnp utilizing Confocal Laser Scanning Microscopy, Scanning Electron Microscopy and colony-forming units from pulverized dentin. Phase-2: The interaction of post-treatment biofilm and RAW macrophages was evaluated regarding pro/anti-inflammatory markers, cell viability and spreading at 24, 48 and 72 h. Compared to conventionally disinfected six-week-old biofilm, CSnp resulted in less viable bacteria (p < 0.01). Scanning electron micrographs demonstrated disruption of the biofilm. CSnp exhibited less residual bacterial load in pulverized dentin (p < 0.001). Macrophage interaction with CSnp-treated biofilm reduced proinflammatory markers (nitric oxide, TNF-?, IL-1?, and IL-6), increased anti-inflammatory marker (TGF-?1) and enhanced cell survival and spreading over time (p < 0.01 at 72 h). Engineered chitosan nanoparticles concurrently inactivated biofilm and altered the inflammatory response of macrophages that would promote healing.

SUBMITTER: Hussein H

PROVIDER: S-EPMC7141246 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Antibiofilm and Immune Response of Engineered Bioactive Nanoparticles for Endodontic Disinfection.

Hussein Hebatullah H Kishen Anil A

Journal of clinical medicine 20200309 3

The biological aim of root canal treatment is to facilitate periapical tissue healing following endodontic therapy. This study aimed to develop an organotypic infected root canal model to understand the interaction of bacterial biofilm with macrophages and study the therapeutic effect of engineered bioactive chitosan nanoparticles (CSnp) on macrophages. Ex-vivo experiments were conducted in two phases; Phase-1: <i>Enterococcus faecalis</i> biofilms (two and six weeks old) developed in organotypi ...[more]

PMID: 32182743

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Project description:Antimicrobial-resistant infections are an urgent public health threat, and development of novel antimicrobial therapies has been painstakingly slow. Polymicrobial infections are increasingly recognized as a significant source of severe disease and also contribute to reduced susceptibility to antimicrobials. Chronic infections also are characterized by their ability to resist clearance, which is commonly linked to the development of biofilms that are notorious for antimicrobial resistance. The use of engineered cationic antimicrobial peptides (eCAPs) is attractive due to the slow development of resistance to these fast-acting antimicrobials and their ability to kill multidrug-resistant clinical isolates, key elements for the success of novel antimicrobial agents. Here, we tested the ability of an eCAP, WLBU2, to disrupt recalcitrant Pseudomonas aeruginosa biofilms. WLBU2 was capable of significantly reducing biomass and viability of P. aeruginosa biofilms formed on airway epithelium and maintained activity during viral coinfection, a condition that confers extraordinary levels of antibiotic resistance. Biofilm disruption was achieved in short treatment times by permeabilization of bacterial membranes. Additionally, we observed simultaneous reduction of infectivity of the viral pathogen respiratory syncytial virus (RSV). WLBU2 is notable for its ability to maintain activity across a broad range of physiological conditions and showed negligible toxicity toward the airway epithelium, expanding its potential applications as an antimicrobial therapeutic. IMPORTANCE Antimicrobial-resistant infections are an urgent public health threat, making development of novel antimicrobials able to effectively treat these infections extremely important. Chronic and polymicrobial infections further complicate antimicrobial therapy, often through the development of microbial biofilms. Here, we describe the ability of an engineered antimicrobial peptide to disrupt biofilms formed by the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogen Pseudomonas aeruginosa during coinfection with respiratory syncytial virus. We also observed antiviral activity, indicating the ability of engineered antimicrobial peptides to act as cross-kingdom single-molecule combination therapies.

Dataset Information

Antibiofilm and Immune Response of Engineered Bioactive Nanoparticles for Endodontic Disinfection.

Publications

Antibiofilm and Immune Response of Engineered Bioactive Nanoparticles for Endodontic Disinfection.

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