Does nanocrystalline silver have a transferable effect?
Patricia L. Nadworny BSc
Department of Chemical and Materials Engineering,
Department of Biomedical Engineering and
Search for more papers by this authorBreanne K. Landry BSc
Department of Chemical and Materials Engineering,
Search for more papers by this authorJianFei Wang PhD
Department of Surgery, University of Alberta, Edmonton, AB, Canada
Search for more papers by this authorEdward E. Tredget MD, MSc
Department of Surgery, University of Alberta, Edmonton, AB, Canada
Search for more papers by this authorRobert E. Burrell PhD
Department of Chemical and Materials Engineering,
Department of Biomedical Engineering and
Search for more papers by this authorPatricia L. Nadworny BSc
Department of Chemical and Materials Engineering,
Department of Biomedical Engineering and
Search for more papers by this authorBreanne K. Landry BSc
Department of Chemical and Materials Engineering,
Search for more papers by this authorJianFei Wang PhD
Department of Surgery, University of Alberta, Edmonton, AB, Canada
Search for more papers by this authorEdward E. Tredget MD, MSc
Department of Surgery, University of Alberta, Edmonton, AB, Canada
Search for more papers by this authorRobert E. Burrell PhD
Department of Chemical and Materials Engineering,
Department of Biomedical Engineering and
Search for more papers by this authorABSTRACT
This study examined the mechanism of nanocrystalline silver antiinflammatory activity, and tested nanocrystalline silver for systemic antiinflammatory effects. Secondary ion mass spectroscopy of skin treated directly with nanocrystalline silver for 24 hours showed that at skin surfaces there were significant deposits at weights corresponding to Ag, AgO, AgCl, AgNO3, Ag2O, and silver clusters Ag2-6, but silver penetration was minimal. To test for translocation of the effect, a porcine contact dermatitis model in which wounds were induced on one side of the back and then treated with nanocrystalline silver on the opposite side of the back was used. Visual and histological data showed improvement relative to animals treated with saline only. Significantly increased induction of apoptosis in the inflammatory cells present in the dermis was observed with remote nanocrystalline silver treatments. In addition, immunohistochemical analysis showed decreased levels of proinflammatory cytokines tumor necrosis factor-α and interleukin-8, and increased levels of antiinflammatory cytokine interleukin-4, epidermal growth factor, keratinocyte growth factor, and keratinocyte growth factor-2. Thus, the antiinflammatory effects of nanocrystalline silver appear to be induced by interactions with cells in the top layers of the skin, which then release biological signals resulting in widespread antiinflammatory activity.
Supporting Information
Figure S1. Representative images of SIMS detection of summed weights of various silver species deposited in porcine epidermis and upper dermis, with silver species/weights tested as indicated in Table 1. The top row of each image contains Ag, AgO, AgCl, and AgNO3, respectively; the second row of each image contains Ag2, Ag2O, Ag3, and Ag4 respectively; and the third row of each image contains Ag5, Ag6, Ag7, and the sum of all Ag compounds, respectively. Images are shown for (A) negative control animals treated for 24 hours with saline, and for DNCB-induced porcine wounds treated for 24 hours with (B) saline, (C) silver nitrate, or (D) nanocrystalline silver. Optical images are also provided, with the area within the green box being the area scanned for SIMS analysis. mc=maximum count. tc=total count. The coloration of each image is scaled from 0 (black) to the mc for that image (white). Each intensity scale is different, and image intensities should not be compared to one another directly.
Figure S2. Digital images of wounds. (A) Porcine DNCB-induced wound before treatment. (B) Porcine DNCB-induced wound treated with saline only for 24 hours. (C) Porcine DNCB-induced wound treated remotely with nanocrystalline silver for 24 hours. Wound rulers are included to indicate the image scale in centimetres.
Figure S3. Representative images for immunohistochemical detection of TNF-α after 24 hours (column 1) and 72 hours (column 2) treatment of DNCB-induced porcine wounds with saline (A–B), or remote nanocrystalline silver (C–D). Staining for TNF-α appears brown, while the cell nuclei are counterstained purple using hematoxylin.
Figure S4. Representative images for immunohistochemical detection of IL-4 after 24 hours (column 1) and 72 hours (column 2) treatment of DNCB-induced porcine wounds with saline (A–B), or remote nanocrystalline silver (C–D). Staining for IL-4 appears brown, while the cell nuclei are counterstained purple using hematoxylin.
Figure S5. Representative images for immunohistochemical detection of KGF-2 after 24 hours (column 1) and 72 hours (column 2) treatment of DNCB-induced porcine wounds with saline (A–B), or remote nanocrystalline silver (C–D). Staining for KGF-2 appears brown, while the cell nuclei are counterstained purple using hematoxylin.
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