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Polyhexamethylene Biguanide:Polyurethane Blend Nanofibrous Membranes for Wound Infection Control.

ABSTRACT: Polyhexamethylene biguanide (PHMB) is a broad-spectrum antiseptic which avoids many efficacy and toxicity problems associated with antimicrobials, in particular, it has a low risk of loss of susceptibility due to acquired antimicrobial resistance. Despite such advantages, PHMB is not widely used in wound care, suggesting more research is required to take full advantage of PHMB's properties. We hypothesised that a nanofibre morphology would provide a gradual release of PHMB, prolonging the antimicrobial effects within the therapeutic window. PHMB:polyurethane (PU) electrospun nanofibre membranes were prepared with increasing PHMB concentrations, and the effects on antimicrobial activities, mechanical properties and host cell toxicity were compared. Overall, PHMB:PU membranes displayed a burst release of PHMB during the first hour following PBS immersion (50.5-95.9% of total released), followed by a gradual release over 120 h (?25 wt % PHMB). The membranes were hydrophilic (83.7-53.3°), gradually gaining hydrophobicity as PHMB was released. They displayed superior antimicrobial activity, which extended past the initial release period, retained PU hyperelasticity regardless of PHMB concentration (collective tensile modulus of 5-35% PHMB:PU membranes, 3.56 ± 0.97 MPa; ultimate strain, >200%) and displayed minimal human cell toxicity (<25 wt % PHMB). With further development, PHMB:PU electrospun membranes may provide improved wound dressings.

SUBMITTER: Worsley A

PROVIDER: S-EPMC6572704 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Polyhexamethylene Biguanide:Polyurethane Blend Nanofibrous Membranes for Wound Infection Control.

Worsley Anna A Vassileva Kristin K Tsui Janice J Song Wenhui W Good Liam L

Polymers 20190522 5

Polyhexamethylene biguanide (PHMB) is a broad-spectrum antiseptic which avoids many efficacy and toxicity problems associated with antimicrobials, in particular, it has a low risk of loss of susceptibility due to acquired antimicrobial resistance. Despite such advantages, PHMB is not widely used in wound care, suggesting more research is required to take full advantage of PHMB's properties. We hypothesised that a nanofibre morphology would provide a gradual release of PHMB, prolonging the antimi ...[more]

PMID: 31121845

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Project description:Antimicrobial resistance is a critical public health issue that requires a thorough understanding of the factors that influence the selection and spread of antibiotic-resistant bacteria. Biocides, which are widely used in cleaning and disinfection procedures in a variety of settings, may contribute to this resistance by inducing similar defense mechanisms in bacteria against both biocides and antibiotics. However, the strategies used by bacteria to adapt and develop cross-resistance remain poorly understood, particularly within biofilms -a widespread bacterial habitat that significantly influences bacterial tolerance and adaptive strategies. Using a combination of adaptive laboratory evolution experiments, genomic and RT-qPCR analyses, and biofilm structural characterization using confocal microscopy, we investigated in this study how Escherichia coli biofilms adapted after 28 days of exposure to three biocidal active substances and the effects on cross-resistance to antibiotics. Interestingly, polyhexamethylene biguanide (PHMB) exposure led to an increase of gentamicin resistance (GenR) phenotypes in biofilms formed by most of the seven E. coli strains tested. Nevertheless, most variants that emerged under biocidal conditions did not retain the GenR phenotype after removal of antimicrobial stress, suggesting a transient adaptation (adaptive resistance). The whole genome sequencing of variants with stable GenR phenotypes revealed recurrent mutations in genes associated with cellular respiration, including cytochrome oxidase (cydA, cyoC) and ATP synthase (atpG). RT-qPCR analysis revealed an induction of gene expression associated with biofilm matrix production (especially curli synthesis), stress responses, active and passive transport and cell respiration during PHMB exposure, providing insight into potential physiological responses associated with adaptive crossresistance. In addition, confocal laser scanning microscopy (CLSM) observations demonstrated a global effect of PHMB on biofilm architectures and compositions formed by most E. coli strains, with the appearance of dense cellular clusters after a 24h-exposure. In conclusion, our results showed that the PHMB exposure stimulated the emergence of an adaptive cross-resistance to gentamicin in biofilms, likely induced through the activation of physiological responses and biofilm structural modulations altering gradients and microenvironmental conditions in the biological edifice.

Dataset Information

Polyhexamethylene Biguanide:Polyurethane Blend Nanofibrous Membranes for Wound Infection Control.

Publications

Polyhexamethylene Biguanide:Polyurethane Blend Nanofibrous Membranes for Wound Infection Control.

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