Toxicity of silver nanoparticles on wound healing: A case study of zebrafish fin regeneration model.

Dressings coated with silver nanoparticle (AgNP) are widely used in the management of acute and chronic wounds. However, whether AgNP exerts toxicity on wound healing remains ambiguous. To demonstrate the effects of AgNP on wound healing, we precisely quantified the recovery speed of wound by taking advantage of the fin regeneration of zebrafish. This method also enabled assessment of the adverse effect of AgNP on various steps of wound healing in vivo. We revealed that AgNP treatment at the concentration of 2 µg/ml impaired fin regeneration when exposure was performed at the phases of epithelialization and the beginning of blastema formation. Cell proliferation of regenerative blastema was significantly decreased after AgNP exposure. But the canonical signals including Wingless/Integrated (Wnt), Notch and Fibroblast growth factor (Fgf) which play important roles in cell proliferation during fin regeneration were not modulated at 36 hours post amputation (hpa). Further study showed that AgNP impaired fin regeneration through declining amputation-induced ROS as early as epithelialized phase at 18 hpa, rather than inducing ROS generation. AgNP exposure also promoted recruitment of neutrophils in the early phase of wound healing, which suggests that this event dampened amputation-induced ROS. Overall, this study suggested that application of AgNP-coated dressings should be carefully considered at the beginning stage of wound healing.