Abstract

Size-controlled spherical silver nanoparticles (<10 nm) and chitin-nanofiber sheet composites (Ag NPs/CNFS) have previously been reported to have strong antimicrobial activity in vitro. Although Ag NPs/CNFS have strong antimicrobial activity, their cytotoxicity has not been investigated. This study was performed to evaluate the effects of Ag NPs/CNFS on cytotoxicity for fibroblasts in vitro and healing delay of wound repair in vivo, focused on oxidative stress. Cytotoxic activities of Ag NPs/CNFS were investigated using a fibroblast cell proliferation assay, nitric oxide/nitrogen dioxide (NO/NO2) measurement of the cell lysates in vitro, inhibitory effects of Ag NPs/CNFS on healing-impaired wound repair using diabetic mice in vivo, 8-hydroxy-2′-deoxyguanosine (8-OHdG) immunohistochemical staining of the skin sections, and generation of carbonyl protein in the wound was performed to evaluate cytotoxicity with oxidative stress. Ag NPs/CNFS exhibited cytotoxicity for fibroblasts and a significant increase of total NO/NO2 levels in the cell lysates in vitro and increased levels of 8-OHdG and carbonyl proteins in vivo. Although wound repair in the continuously Ag NPs/CNFS-treated group was delayed, it could be mitigated by washing the covered wound with saline. Thus, Ag NPs/CNFS may become accepted as an anti-infectious wound dressing.

Highlights

  • Interest in silver nanoparticles (Ag NPs) and their applications has increased, mainly because of their antimicrobial activities, allowing their use in commercial products such as personal care, household, and medical products as well as in textiles and food products [1,2]

  • The proposed mechanism by which Ag NPs lead to cytotoxicity has been considered to at least partially be through the induction of reactive oxygen species (ROS) [11,14]

  • Despite the acceptance of chitin/chitosan as a suitable biocompatible carrier agent for Ag NPs [27,29], no study has investigated the cytotoxicity of Ag NPs/chitin-nanofiber sheets (CNFS)

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Summary

Introduction

Interest in silver nanoparticles (Ag NPs) and their applications has increased, mainly because of their antimicrobial activities, allowing their use in commercial products such as personal care, household, and medical products as well as in textiles and food products [1,2]. Biological and environmental risks of synthetic Ag NPs include adverse effects on some aquatic organisms, including cytotoxicity and genotoxicity in fish [7] and inhibition of photosynthesis in algae [8]. The evaluation of cytotoxicity of Ag NPs has been carried out in different cellular models [1], including lung fibroblasts [10], glioblastoma cells [10], lung cancer cell line [11], hepatocytes [12], and mesenchymal stem cells [13]. The proposed mechanism by which Ag NPs lead to cytotoxicity has been considered to at least partially be through the induction of reactive oxygen species (ROS) [11,14]

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