Abstract
Biofilm-associated infections are a major cause of impaired wound healing. Despite the broad spectrum of anti-bacterial benefits provided by silver nanoparticles (AgNPs), these materials still cause controversy due to cytotoxicity and a lack of efficacy against mature biofilms. Herein, highly potent ultrasmall AgNPs were combined with a biocompatible hydrogel with integrated synergistic functionalities to facilitate elimination of clinically relevant mature biofilms in-vivo combined with improved wound healing capacity. The delivery platform showed a superior release mechanism, reflected by high biocompatibility, hemocompatibility, and extended antibacterial efficacy. In vivo studies using the S. aureus wound biofilm model showed that the AgNP hydrogel (200 µg/g) was highly effective in eliminating biofilm infection and promoting wound repair compared to the controls, including silver sulfadiazine (Ag SD). Treatment of infected wounds with the AgNP hydrogel resulted in faster wound closure (46% closure compared to 20% for Ag SD) and accelerated wound re-epithelization (60% for AgNP), as well as improved early collagen deposition. The AgNP hydrogel did not show any toxicity to tissue and/or organs. These findings suggest that the developed AgNP hydrogel has the potential to be a safe wound treatment capable of eliminating infection and providing a safe yet effective strategy for the treatment of infected wounds.
Highlights
Wound infection is a major medical threat as continuous colonization of pathogens impairs healing and can leads to sepsis [1,2]
This study investigated the efficacy of a controlled release system of ultrasmall AgNPs against mature and clinically relevant S. aureus biofilms using a validated model of mature biofilm wound infection
Utilizing the inherent nature of water-soluble polymeric hydrogel as a tissue scaffold and integrated thermoresponsive functionality as a controlled release mechanism of ultrasmall AgNPs [30,31], for the first time, we demonstrated the ability of topically administered AgNP hydrogel to clear mature S. aureus biofilms and promote wound healing simultaneously (Scheme 1)
Summary
Wound infection is a major medical threat as continuous colonization of pathogens impairs healing and can leads to sepsis [1,2]. Chronic wounds provide a fertile environment for the development of mature biofilms, which offer bacteria protection from antibiotics or host defence proteins [3,4]. Staphylococcus aureus (S. aureus) bacteria has been identified as a leading cause of wound infection with the ability to develop multiple-antibiotic resistance and lead to chronic infections that are hard to combat [5]. Application of higher doses of therapeutic agents is often required for the complete elimination of pathogens because the physical and metabolic barriers provided by biofilms lead to high resistance and poor penetrations of antimicrobials [6]. Treatment strategies aimed at the mitigation of bacterial biofilms with the capacity to promote healing have attracted significant attention
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