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      Sprayable and biodegradable, intrinsically adhesive wound dressing with antimicrobial properties

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          Abstract

          Conventional wound dressings are difficult to apply to large total body surface area (TBSA) wounds, as they typically are prefabricated, require a layer of adhesive coating for fixation, and need frequent replacement for entrapped exudate. Large TBSA wounds as well as orthopedic trauma and low‐resource surgery also have a high risk of infection. In this report, a sprayable and intrinsically adhesive wound dressing loaded with antimicrobial silver is investigated that provides personalized fabrication with minimal patient contact. The dressing is composed of adhesive and biodegradable poly(lactic‐ co‐glycolic acid) and poly(ethylene glycol) (PLGA/PEG) blend fibers with or without silver salt (AgNO 3). in vitro studies demonstrate that the PLGA/PEG/Ag dressing has antimicrobial properties and low cytotoxicity, with antimicrobial silver controllably released over 7–14 days. In a porcine partial‐thickness wound model, the wounds treated with both antimicrobial and nonantimicrobial PLGA/PEG dressings heal at rates similar to those of the clinical, thin film polyurethane wound dressing, with similar scarring. However, PLGA/PEG adds a number of features beneficial for wound healing: greater exudate absorption, integration into the wound, a 25% reduction in dressing changes, and tissue regeneration with greater vascularization. There is also modest improvement in epidermis thickness compared to the control wound dressing.

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          Most cited references48

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          Polymeric system for dual growth factor delivery.

          The development of tissues and organs is typically driven by the action of a number of growth factors. However, efforts to regenerate tissues (e.g., bone, blood vessels) typically rely on the delivery of single factors, and this may partially explain the limited clinical utility of many current approaches. One constraint on delivering appropriate combinations of factors is a lack of delivery vehicles that allow for a localized and controlled delivery of more than a single factor. We report a new polymeric system that allows for the tissue-specific delivery of two or more growth factors, with controlled dose and rate of delivery. The utility of this system was investigated in the context of therapeutic angiogenesis. We now demonstrate that dual delivery of vascular endothelial growth factor (VEGF)-165 and platelet-derived growth factor (PDGF)-BB, each with distinct kinetics, from a single, structural polymer scaffold results in the rapid formation of a mature vascular network. This is the first report of a vehicle capable of delivery of multiple angiogenic factors with distinct kinetics, and these results clearly indicate the importance of multiple growth factor action in tissue regeneration and engineering.
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            Innate immune responses to trauma

            Trauma can affect any individual at any location and at any time over a lifespan. The disruption of macrobarriers and microbarriers induces instant activation of innate immunity. The subsequent complex response, designed to limit further damage and induce healing, also represents a major driver of complications and fatal outcome after injury. This Review aims to provide basic concepts about the posttraumatic response and is focused on the interactive events of innate immunity at frequent sites of injury: the endothelium at large, and sites within the lungs, inside and outside the brain and at the gut barrier.
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              Silver enhances antibiotic activity against gram-negative bacteria.

              A declining pipeline of clinically useful antibiotics has made it imperative to develop more effective antimicrobial therapies, particularly against difficult-to-treat Gram-negative pathogens. Silver has been used as an antimicrobial since antiquity, yet its mechanism of action remains unclear. We show that silver disrupts multiple bacterial cellular processes, including disulfide bond formation, metabolism, and iron homeostasis. These changes lead to increased production of reactive oxygen species and increased membrane permeability of Gram-negative bacteria that can potentiate the activity of a broad range of antibiotics against Gram-negative bacteria in different metabolic states, as well as restore antibiotic susceptibility to a resistant bacterial strain. We show both in vitro and in a mouse model of urinary tract infection that the ability of silver to induce oxidative stress can be harnessed to potentiate antibiotic activity. Additionally, we demonstrate in vitro and in two different mouse models of peritonitis that silver sensitizes Gram-negative bacteria to the Gram-positive-specific antibiotic vancomycin, thereby expanding the antibacterial spectrum of this drug. Finally, we used silver and antibiotic combinations in vitro to eradicate bacterial persister cells, and show both in vitro and in a mouse biofilm infection model that silver can enhance antibacterial action against bacteria that produce biofilms. This work shows that silver can be used to enhance the action of existing antibiotics against Gram-negative bacteria, thus strengthening the antibiotic arsenal for fighting bacterial infections.
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                Author and article information

                Contributors
                kofinas@umd.edu
                Journal
                Bioeng Transl Med
                Bioeng Transl Med
                10.1002/(ISSN)2380-6761
                BTM2
                Bioengineering & Translational Medicine
                John Wiley & Sons, Inc. (Hoboken, USA )
                2380-6761
                13 December 2019
                January 2020
                : 5
                : 1 ( doiID: 10.1002/btm2.v5.1 )
                : e10149
                Affiliations
                [ 1 ] Fischell Department of Bioengineering University of Maryland College Park Maryland
                [ 2 ] Sheikh Zayed Institute for Pediatric Surgical Innovation Joseph E. Robert Jr. Center for Surgical Care, Children's National Medical Center Washington District of Columbia
                [ 3 ] Department of Chemical and Biomolecular Engineering University of Maryland College Park Maryland
                [ 4 ] Department of Chemistry and Biochemistry University of Maryland College Park Maryland
                Author notes
                [*] [* ] Correspondence

                Peter Kofinas, Department of Chemical and Biomolecular Engineering, University of Maryland, 4418 Stadium Dr., College Park, MD 20742.

                Email: kofinas@ 123456umd.edu

                Author information
                https://orcid.org/0000-0001-6657-3037
                Article
                BTM210149
                10.1002/btm2.10149
                6971445
                31989038
                c688e905-569a-4ef3-9ae7-67ea5ddd97b2
                © 2019 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals, Inc. on behalf of The American Institute of Chemical Engineers.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 04 July 2019
                : 04 November 2019
                : 03 December 2019
                Page count
                Figures: 8, Tables: 0, Pages: 12, Words: 9264
                Funding
                Funded by: National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health
                Award ID: F31EB025735
                Award ID: R01EB019963
                Categories
                Research Report
                Research Reports
                Custom metadata
                2.0
                January 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.5 mode:remove_FC converted:21.01.2020

                antimicrobial wound dressings,biodegradable polymers,silver,solution blow spinning,wound healing

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