Purpose for healing of large skin defects is a signi?cant clinical challenge.The recent emergence of silver nanoparticles has provided a new therapeutic method for burn wounds but the mechanism remains unknown.Method and ressult: In this study, we demonstrated that a metallic nanosilver particlescollagen/chitosan hybrid scaffold (NAg-CCS) (with a size of 20-40 nm and concentration of 10 ppm) with strong antibacterial and anti-inflammatory properties could promote wound healing with inhibited scarring.In vitro the scratch assay demonstrated the NAg with a concentration of 10ppm not only didn't influence the activity of human derived keratinocyte (HaCaT cell) but also improve the migration of fibroblasts.The immunofluorescent staining confirmed the fibroblasts treated with NAg presented an increased expression of α-smooth muscle actin (α-SMA).Antibacterial activity of NAg-CCS was also evaluated.In vivo, the NAg-CCS was applied in the skin defects of Sprague-Dawley (SD) rat confirmed the in vivo mediation of infiammatory factors expression by immunohistochemistry, real-time quantitative PCR (RT-qPCR) and western blotting during 28 d post-surgery.The levels of other pro-inflammatory and scar-related factors such as CD68, tumor necrosis factor-α (TNF-α), transforming growth factor beta (TGF-β) and interleukin-6 (IL-6) were down-regulated while that of interleukin-10 (IL-10) and interferon-y (IFN-y) were increased.The α -SMA of wound section was also up-regulated.In combination with the ultra-thin skin graft transplantation for 60 d, the regenerated skin by NAg-CCS had an extremely similar structure to normal one.Disscusion:Our results indicate that NAg-CCS is anti-inflammatory and bactericidal without discernible in vitro or in vivo cytotoxicity or negative effects onfibroblast cells, making the scaffold an ideal dermal substitute for wound regeneration.