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      Toward a Closed Loop, Integrated Biocompatible Biopolymer Wound Dressing Patch for Detection and Prevention of Chronic Wound Infections

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          Abstract

          Chronic wound infections represent a significant burden to healthcare providers globally. Often, chronic wound healing is impeded by the presence of infection within the wound or wound bed. This can result in an increased healing time, healthcare cost and poor patient outcomes. Thus, there is a need for dressings that help the wound heal, in combination with early detection of wound infections to support prompt treatment. In this study, we demonstrate a novel, biocompatible wound dressing material, based on Polyhydroxyalkanoates, doped with graphene platelets, which can be used as an electrochemical sensing substrate for the detection of a common wound pathogen, Pseudomonas aeruginosa. Through the detection of the redox active secondary metabolite, pyocyanin, we demonstrate that a dressing can be produced that will detect the presence of pyocyanin across clinically relevant concentrations. Furthermore, we show that this sensor can be used to identify the presence of pyocyanin in a culture of P. aeruginosa. Overall, the sensor substrate presented in this paper represents the first step toward a new dressing with the capacity to promote wound healing, detect the presence of infection and release antimicrobial drugs, on demand, to optimized healing.

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          Most cited references60

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          Antibacterial activity and mechanism of action of the silver ion in Staphylococcus aureus and Escherichia coli.

          The antibacterial effect and mechanism of action of a silver ion solution that was electrically generated were investigated for Staphylococcus aureus and Escherichia coli by analyzing the growth, morphology, and ultrastructure of the bacterial cells following treatment with the silver ion solution. Bacteria were exposed to the silver ion solution for various lengths of time, and the antibacterial effect of the solution was tested using the conventional plate count method and flow cytometric (FC) analysis. Reductions of more than 5 log(10) CFU/ml of both S. aureus and E. coli bacteria were confirmed after 90 min of treatment with the silver ion solution. Significant reduction of S. aureus and E. coli cells was also observed by FC analysis; however, the reduction rate determined by FC analysis was less than that determined by the conventional plate count method. These differences may be attributed to the presence of bacteria in an active but nonculturable (ABNC) state after treatment with the silver ion solution. Transmission electron microscopy showed considerable changes in the bacterial cell membranes upon silver ion treatment, which might be the cause or consequence of cell death. In conclusion, the results of the present study suggest that silver ions may cause S. aureus and E. coli bacteria to reach an ABNC state and eventually die.
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            Multiple bacterial species reside in chronic wounds: a longitudinal study.

            The aim of the study was to investigate the bacterial profile of chronic venous leg ulcers and the importance of the profile to ulcer development. Patients with persisting venous leg ulcers were included and followed for 8 weeks. Every second week, ulcer samples were collected and the bacterial species present were identified. More than one bacterial species were detected in all the ulcers. The most common bacteria found were Staphylococcus aureus (found in 93.5% of the ulcers), Enterococcus faecalis (71.7%), Pseudomonas aeruginosa (52.2%), coagulase-negative staphylococci (45.7%), Proteus species (41.3%) and anaerobic bacteria (39.1%). Resident bacterial species were present in all the ulcers. In 76% of the ulcers, two or more (up to five) resident bacterial species were found. The most common resident bacterial species were S. aureus and P. aeruginosa. Furthermore, ulcers with P. aeruginosa were found to be significantly larger than ulcers without the presence of P. aeruginosa (P < 0.005). Our study demonstrated that the chronic wound is colonised by multiple bacterial species and that once they are established many of them persist in the wound. Our results suggest that the presence of P. aeruginosa in venous leg ulcers can induce ulcer enlargement and/or cause delayed healing.
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              Distribution, organization, and ecology of bacteria in chronic wounds.

              Between 1 and 2% of the population in the developed world experiences a nonhealing or chronic wound characterized by an apparent arrest in a stage dominated by inflammatory processes. Lately, research groups have proposed that bacteria might be involved in and contribute to the lack of healing of these wounds. To investigate this, we collected and examined samples from chronic wounds obtained from 22 different patients, all selected because of suspicion of Pseudomonas aeruginosa colonization. These wound samples were investigated by standard culturing methods and peptide nucleic acid-based fluorescence in situ hybridization (PNA FISH) for direct identification of bacteria. By means of the culturing methods, Staphylococcus aureus was detected in the majority of the wounds, whereas P. aeruginosa was observed less frequently. In contrast, using PNA FISH, we found that a large fraction of the wounds contained P. aeruginosa. Furthermore, PNA FISH revealed the structural organization of bacteria in the samples. It appeared that P. aeruginosa aggregated as microcolonies imbedded in the matrix component alginate, which is a characteristic hallmark of the biofilm mode of growth. The present investigation suggests that bacteria present within these wounds tend to be aggregated in microcolonies imbedded in a self-produced matrix, characteristic of the biofilm mode of growth. Additionally, we must conclude that there exists no good correlation between bacteria detected by standard culturing methods and those detected by direct detection methods such as PNA FISH. This strongly supports the development of new diagnostic and treatment strategies for chronic wounds.
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                Author and article information

                Contributors
                Journal
                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                2296-4185
                01 September 2020
                2020
                : 8
                : 1039
                Affiliations
                [1] 1Department of Biomedical Engineering, Faculty of Engineering, University of Strathclyde , Glasgow, United Kingdom
                [2] 2School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster , London, United Kingdom
                [3] 3Vivisco Pvt Ltd , London, United Kingdom
                [4] 4School of Mechanical Engineering, Faculty of Engineering, University of Leeds , Leeds, United Kingdom
                [5] 5School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds , Leeds, United Kingdom
                [6] 6Department of Materials Science and Engineering, Faculty of Engineering, The University of Sheffield , Sheffield, United Kingdom
                Author notes

                Edited by: Elisa Mele, Loughborough University, United Kingdom

                Reviewed by: Rosalia Bertorelli, Italian Institute of Technology (IIT), Italy; Giulia Suarato, Italian Institute of Technology (IIT), Italy

                *Correspondence: Ipsita Roy, I.Roy@ 123456sheffield.ac.uk

                This article was submitted to Nanobiotechnology, a section of the journal Frontiers in Bioengineering and Biotechnology

                Article
                10.3389/fbioe.2020.01039
                7493637
                51b70682-4f69-4b20-b97c-d88d917afe64
                Copyright © 2020 Ward, Dubey, Basnett, Lika, Newman, Corrigan, Russell, Kim, Chakrabarty, Connolly and Roy.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 29 April 2020
                : 11 August 2020
                Page count
                Figures: 7, Tables: 0, Equations: 0, References: 71, Pages: 12, Words: 0
                Categories
                Bioengineering and Biotechnology
                Original Research

                wound dressing,biopolymer,pyocyanin,pseudomonas aeruginosa,graphene,polyhydroxyalkanoates,artificial intelligence,electrochemical

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