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      A New Dermal Substitute Containing Polyvinyl Alcohol with Silver Nanoparticles and Collagen with Hyaluronic Acid: In Vitro and In Vivo Approaches

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          Abstract

          The experimental use of poly (alcohol-vinyl) (PVA) as a skin curative is increasing widely. However, the use of this hydrogel is challenging due to its favorable properties for microbiota growth. The association with silver nanoparticles (AgNPs) as an antimicrobial agent turns the match for PVA as a dressing, as it focuses on creating a physical barrier to avoid wound dehydration. When associated with extracellular components, such as the collagen matrix, the device obtained can create the desired biological conditions to act as a skin substitute. This study aimed to analyze the anti-microbiological activity and the in vitro and in vivo responses of a bilaminar device of PVA containing AgNPs associated with a membrane of collagen–hyaluronic acid (col-HA). Additionally, mesenchymal stem cells were cultured in the device to evaluate in vitro responses and in vivo immunomodulatory and healing behavior. The device morphology revealed a porous pattern that favored water retention and in vitro cell adhesion. Controlled wounds in the dorsal back of rat skins revealed a striking skin remodeling with new epidermis fulfilling all previously injured areas after 14 and 28 days. No infections or significant inflammations were observed, despite increased angiogenesis, and no fibrosis-markers were identified as compared to controls. Although few antibacterial activities were obtained, the addition of AgNPs prevented fungal growth. All results demonstrated that the combination of the components used here as a dermal device, chosen according to previous miscellany studies of low/mid-cost biomaterials, can promote skin protection avoiding infections and dehydration, minimize the typical wound inflammatory responses, and favor the cellular healing responses, features that give rise to further clinical trials of the device here developed

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          Most cited references43

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          A mechanistic study of the antibacterial effect of silver ions onEscherichia coli andStaphylococcus aureus

          To investigate the mechanism of inhibition of silver ions on microorganisms, two strains of bacteria, namely Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus), were treated with AgNO(3) and studied using combined electron microscopy and X-ray microanalysis. Similar morphological changes occurred in both E. coli and S. aureus cells after Ag(+) treatment. The cytoplasm membrane detached from the cell wall. A remarkable electron-light region appeared in the center of the cells, which contained condensed deoxyribonucleic acid (DNA) molecules. There are many small electron-dense granules either surrounding the cell wall or depositing inside the cells. The existence of elements of silver and sulfur in the electron-dense granules and cytoplasm detected by X-ray microanalysis suggested the antibacterial mechanism of silver: DNA lost its replication ability and the protein became inactivated after Ag(+) treatment. The slighter morphological changes of S. aureus compared with E. coli recommended a defense system of S. aureus against the inhibitory effects of Ag(+) ions. Copyright 2000 John Wiley & Sons, Inc.
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            The myofibroblast in wound healing and fibrocontractive diseases.

            G Gabbiani (2003)
            The demonstration that fibroblastic cells acquire contractile features during the healing of an open wound, thus modulating into myofibroblasts, has open a new perspective in the understanding of mechanisms leading to wound closure and fibrocontractive diseases. Myofibroblasts synthesize extracellular matrix components such as collagen types I and III and during normal wound healing disappear by apoptosis when epithelialization occurs. The transition from fibroblasts to myofibroblasts is influenced by mechanical stress, TGF-beta and cellular fibronectin (ED-A splice variant). These factors also play important roles in the development of fibrocontractive changes, such as those observed in liver cirrhosis, renal fibrosis, and stroma reaction to epithelial tumours. Copyright 2003 John Wiley & Sons, Ltd.
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              Concise review: role of mesenchymal stem cells in wound repair.

              Wound healing requires a coordinated interplay among cells, growth factors, and extracellular matrix proteins. Central to this process is the endogenous mesenchymal stem cell (MSC), which coordinates the repair response by recruiting other host cells and secreting growth factors and matrix proteins. MSCs are self-renewing multipotent stem cells that can differentiate into various lineages of mesenchymal origin such as bone, cartilage, tendon, and fat. In addition to multilineage differentiation capacity, MSCs regulate immune response and inflammation and possess powerful tissue protective and reparative mechanisms, making these cells attractive for treatment of different diseases. The beneficial effect of exogenous MSCs on wound healing was observed in a variety of animal models and in reported clinical cases. Specifically, they have been successfully used to treat chronic wounds and stimulate stalled healing processes. Recent studies revealed that human placental membranes are a rich source of MSCs for tissue regeneration and repair. This review provides a concise summary of current knowledge of biological properties of MSCs and describes the use of MSCs for wound healing. In particular, the scope of this review focuses on the role MSCs have in each phase of the wound-healing process. In addition, characterization of MSCs containing skin substitutes is described, demonstrating the presence of key growth factors and cytokines uniquely suited to aid in wound repair.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Antibiotics (Basel)
                Antibiotics (Basel)
                antibiotics
                Antibiotics
                MDPI
                2079-6382
                19 June 2021
                June 2021
                : 10
                : 6
                : 742
                Affiliations
                [1 ]Faculty of Medical Sciences and Health, Pontifical Catholic University of São Paulo (PUC/SP), São Paulo 18030-070, Brazil; mendeda3@ 123456gmail.com (D.M.J.); mahausen@ 123456pucsp.br (M.A.H.); dkomatsu@ 123456pucsp.br (D.K.)
                [2 ]Faculty of Mechanical Engineering, State University of Campinas (UNICAMP), São Paulo 13083-860, Brazil; jessicaasami@ 123456gmail.com
                [3 ]Instituto de Medicina Tropical, Universidade de São Paulo (USP), São Paulo 05403-000, Brazil; akemi.higa@ 123456usp.br
                [4 ]Department of Physics, Chemistry and Mathematics, Federal University of São Carlos (UFSCar), São Paulo 18052-780, Brazil; fabioleite@ 123456ufscar.br (F.L.L.); gpmambrini@ 123456ufscar.br (G.P.M.)
                [5 ]Applied Physics Department, Brazilian Center of Physics Research (CBPF), Rio de Janeiro 22290-180, Brazil; andrelinharesrossi@ 123456gmail.com
                Author notes
                Author information
                https://orcid.org/0000-0002-5834-2463
                https://orcid.org/0000-0002-7131-4045
                https://orcid.org/0000-0002-6171-9305
                https://orcid.org/0000-0001-8943-5876
                https://orcid.org/0000-0002-9920-4411
                https://orcid.org/0000-0001-6327-7363
                Article
                antibiotics-10-00742
                10.3390/antibiotics10060742
                8235042
                34205394
                a0022eb7-0846-4b3a-b147-aac78376709c
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 31 May 2021
                : 17 June 2021
                Categories
                Article

                polyvinyl alcohol,silver nanoparticles,dermal substitute,wound healing

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