Nanofiber scaffolds attenuate collagen synthesis of human dermal fibroblasts through TGF-β1/TSG-6 pathway*

Abstract Nanofiber scaffolds are promising patches for skin tissue regeneration as they provide favorable environment for the adhesion, infiltration and proliferation of skin dermal fibroblasts. However, the effects of nanofiber scaffolds on scar formation remain to be elucidated. The aim of this study was to find out the relationship between nanofiber scaffolds and scar formation, along with the underlying mechanism. We found that polycaprolactone (PCL)/gelatin nanofiber scaffolds attenuated the mRNA expression of fibrosis-associated genes in fibroblasts, including collagen I (collagen type I alpha 1), collagen III (collagen type III alpha 1) and fibronectin. Specifically thicker scaffolds displayed stronger fibrosis inhibitory effect than thin scaffolds. The mechanism relied on TGF-β1/TSG-6 pathway, and overexpression of TSG-6 impaired the anti-fibrosis effect of nanofiber scaffolds, which decreased TGF-β1 expression with thickness-dependency. Moreover, in vivo study demonstrated that nanofiber scaffolds remarkably accelerated the wound healing process by reducing the ratios of collagen I/collagen III and TGF-β1, eventually decreased the deposition of collagens. Taken together, our results suggested that the attenuation of fibrosis by PCL/gelatin nanofiber scaffolds was TGF-β1-dependent and through TGF-β1/TSG-6 pathway. Nanofiber scaffold of appropriate thickness would accelerate skin wound healing, stimulate re-epithelialization and form cutaneous skin appendages in skin trauma. Thus, PCL/gelatin nanofiber scaffolds could be adopted for scar-free skin wound healing and skin cosmetics applications.