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Low concentrations of silver nanoparticles have a beneficial effect on wound healing in vitro

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Abstract

Silver has been used in medical application for its antibacterial, antifungal, and anti-inflammatory effects. Silver nanoparticles (AgNPs) are currently in the spotlight. It was shown that their application can be useful in the management of wounds. Our study was conducted to determine whether AgNPs (average size 10.43 ± 4.74 nm) and ionic silver (Ag-I) could affect the wound healing in the in vitro model of normal human dermal fibroblasts (NHDF). We evaluated their effect on reactive oxygen species (ROS) generation and the expression of key transcription factors that coordinate the cellular response to oxidative stress [nuclear factor (erythroid-derived 2)-like 2 (Nrf2)] and inflammation [nuclear factor-κB (NF-κB)], expression of heme oxygenase-1 (HO-1), and interleukin-6 (IL-6) level. Isolated primary NHDF were scratched, heated (1 h; 42 °C), and cultured with AgNPs (0.25, 2.5, and 25 μg/ml) and Ag-I (0.025, 0.1, and 0.25 μg/ml) for 8 or 24 h. The ROS generation, Nrf2, NF-κB, and HO-1 protein expression and IL-6 protein level were then evaluated by standard methods. Non-cytotoxic concentrations of AgNPs (0.25 and 2.5 μg/ml) did not affect the ROS generation but activated the Nrf2/HO-1 pathway and decreased the NF-κB expression and IL-6 level in the in vitro wound healing model. AgNPs at concentrations of 0.25 and 2.5 μg/ml seem to be suitable for the intended application as a topical agent for wound healing, although the gene silencing technique, chemical inhibitors, and detailed time- and concentration-dependent experiments are needed for a comprehensive study of signaling pathway regulation. Further investigation is also necessary to exclude any possible adverse effects.

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Abbreviations

AgNPs:

Silver nanoparticles

Ag-I:

Ionic silver

AP-1:

Activating protein

COX-2:

Cyclooxygenase-2

DMEM:

Dulbecco’s modified Eagle’s medium

HO-1:

Heme oxygenase-1

IL:

Interleukin

NF-κB:

Nuclear factor-kappa B

NHDF:

Normal human dermal fibroblasts

Nrf2:

Nuclear factor (erythroid-derived 2)-like 2

PBS:

Phosphate-buffered saline

TNF-α:

Tumor necrosis factor α

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Acknowledgements

We would like to thank Dr. Alena Rajnochová for a critical review of the manuscript. This work was supported by the grants from Palacký University (IGA_ LF_2015_007 and IGA_LF_2016_012), from the Ministry of Health of the Czech Republic (IGA 15-27726A), and by the National Programme for Sustainability I (L01304).

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Correspondence to Adéla Galandáková.

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Ambrožová, N., Zálešák, B., Ulrichová, J. et al. Low concentrations of silver nanoparticles have a beneficial effect on wound healing in vitro. J Nanopart Res 19, 108 (2017). https://doi.org/10.1007/s11051-017-3809-7

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