Silk-fibroin-based nanofibrous scaffolds integrated with nano-engineered living bacteria enabling antibiotic-free accelerated infected wound healing

Abstract

Bacteria‐infected skin wounds are an immense public health challenge for high mortality-rate and enormous financial burden worldwide. Emerging living bacterial therapy promises the desired therapeutic efficacy for wound healing, however, its indiscriminate negative effects on the bioactivity of beneficial bacteria remain enormous challenges for clinical far-ranging applications. Herein, silk fibroin-based nanofibrous scaffolds equipped with nano-engineered tannic acid (TA)-Fe(III) chelate-encapsulated Lactobacillus reuteri (denoted as Mbr/L@FeTA) were proposed for antibiotic-free accelerated bacteria‐infected wound healing. Mbr/L@FeTA exhibited excellent antimicrobial properties (99.03% and 98.60% bactericidal efficiency against Escherichia coli and Staphylococcus aureus, respectively), gratifying mechanical properties and biocompatibility. Furthermore, due to on-demand TA-Fe(III) chelate-encapsulated bacterial tactics, Mbr/L@FeTA demonstrates exceptional environmental resistance and maintains satisfactory biological-activity even when administered with antibiotics. Additionally, Mbr/L@FeTA enables the stable release of organic acids and other metabolites that significantly improve the wound microenvironment and modulate inflammatory reactions. In vivo and in vitro experiments confirmed that Mbr/L@FeTA strongly promoted cell growth and proliferation, inhibited bacteria growth at the wound-site, and further accelerated the healing process in bacteria-infected wounds. These findings suggest that Mbr/L@FeTA exhibits great potential for applications in antibiotic-free infected wound therapy and simultaneously represents a useful approach for clinical applications of living bacterial therapy.