Multi-drug loaded electrospinning nanofibers promote healing with less scar formation by remodeling wound microenvironment via modulating TGF-β1/Smads/EN1 signal

Abstract

Excessive scar formation following severe burn injury, deep trauma or surgical incision is a critical complication and still is a thorny clinical troublesome, which are mainly characterized by the disordered microenvironment during wound healing. A specialty wound dressing remodeling wound microenvironment is urgently desired. Herein, we fabricate a multi-drug loaded nanofiber delivery system for promoting healing and mitigating scar formation by modulating TGF-β1/Smads/EN1 signal, which encapsulates free rhubarb anthraquinones (RAs) and honey in polyvinylpyrrolidone core layer, and borneol in cellulose acetate shell layer by coaxial electrospinning. The nanofibers exhibited a linear morphology with smooth surface, nanometer in diameter, high porosity, ideal water vapor transmission rate and wettability, a biphasic release profile of RAs with the enhanced dissolution under the synergism of honey and borneol. Furthermore, this nanofiber wound dressing possesses the desired biocompatibility and pro-migration effects on HSF cells and HUVEC, long-term effects against Methicillin-resistant Staphylococcus aureus (MRSA) in vitro, remarkably, promoted healing of the MRSA-infected postsurgical wound and severe burn injury characterized by enhanced closure rates and more hair follicles, and mitigated scar formation characterized by less dermal thickness and more organized collagen arrangement by decreasing the expressions of TGF-β1, Smads2/3 and EN1, and increasing Smad7 expression in wound tissues. Collectively, the findings indicate that the multi-drug loaded nanofiber wound dressing can serve as a promising candidate for the application of MRSA-infected wound and severe burn injury healing.