A multifunctional injectable ε-poly-L-lysine-loaded sodium-alginate/gelatin hydrogel promotes the healing of infected wounds by regulating macrophage polarization and the skin microbiota

Abstract

Background Infected wounds caused by bacteria such as Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) pose significant challenges during the healing process. Hydrogels have emerged as promising materials for the treatment of such infections, as they have the potential to deliver therapeutic agents while supporting tissue repair. Methods In this study, we developed ε-PLL@SA/Gel (PSG) hydrogels by embedding different concentrations of ε-poly-L-lysine (ε-PLL) into sodium alginate (SA)/gelatin (Gel) hydrogels using calcium chloride as a crosslinking agent. The mechanical properties, biocompatibility, antibacterial activity, and wound healing efficacy of the hydrogels were evaluated in vitro and in vivo in mouse models of infected wounds. Results PSG hydrogels exhibited excellent mechanical strength, injectability, and self-adhesive properties. In vitro, hydrogel treatment resulted in high cell viability and promoted human skin fibroblast proliferation. PSG15 exhibited the highest antibacterial activity and inhibited E. coli and S. aureus by 89.53% and 92.21%, respectively. In vivo, PSG15 significantly accelerated wound healing, enhanced angiogenesis, and regulated macrophage polarization by increasing CD206 expression and decreasing CD80 expression. Additionally, PSG15 modulated the skin microbiota, reduced pathogenic bacterial abundance and maintained microbiota diversity. Conclusion The PSG15 hydrogel is a promising candidate for the treatment of infected wounds because it inhibits bacterial growth, promotes tissue repair, and modulates the wound microbiota.