Silver nanoparticles/chitosan oligosaccharide/poly(vinyl alcohol) nanofiber promotes wound healing by activating TGFβ1/Smad signaling pathway

Abstract

Chen-wen Li,1,* Qing Wang,2,* Jing Li,3 Min Hu,1 San-jun Shi,1 Zi-wei Li,1 Guo-lin Wu,1 Huan-huan Cui,1 Yuan-yuan Li,1 Qian Zhang,1 Xiu-heng Yu,2 Lai-chun Lu1 1Department of Pharmacy, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 2College of Pharmacy, Chongqing Medical University, Chongqing, 3Department of Pharmacy, the Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China *These authors contributed equally to this work Abstract: Wound healing occupies a remarkable place in everyday pathology and remains a challenging clinical problem. In our previous study, we prepared a silver nanoparticle/chitosan oligosaccharide/poly(vinyl alcohol) (PVA/COS-AgNPs) nanofiber via electrospinning and revealed that it could promote wound healing; however, the healing mechanism remained unknown. Therefore, we aimed to clarify the mechanism underlying the accelerated healing effect of the PVA/COS-AgNPs nanofiber. The TGFβ1/Smad signaling pathway is actively involved in wound healing. Considering the key role of this signaling pathway in wound healing, our preliminary study showed that the TGFβ1 level was significantly increased during the early stage of wound healing. Thus, in this study, hematoxylin–eosin, Masson’s trichrome, immunofluorescent staining, hydroxyproline content, quantitative real-time polymerase chain reaction, and Western blot analyses were used to analyze the wound healing in a rat model treated with gauze, the PVA/COS-AgNPs nanofiber, and the nanofiber plus SB431542 (an inhibitor of TGFβ1 receptor kinase). The results showed that the PVA/COS-AgNPs nanofiber promoted wound healing and upregulated the expression levels of cytokines associated with the TGFβ1/Smad signaling pathway such as TGFβ1, TGFβRI, TGFβRII, collagen I, collagen III, pSmad2, and pSmad3. Inhibiting this pathway with SB431542 resulted in prevention of the PVA/COS-AgNPs nanofiber-associated salutary effects on the early stage of wound healing and relative cytokines expression. In conclusion, the wound healing effect of the PVA/COS-AgNPs nanofiber involves activation of the TGFβ1/Smad signaling pathway. Keywords: wound healing, electrospinning, nanofiber, silver nanoparticles, TGFβ1, Smad proteins

Keywords

• wound healing
• electrospinning
• nanofiber
• silver nanoparticles
• TGFβ1
• Smad proteins.