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

Infected wounds caused by bacteria such as Escherichia coli and Staphylococcus 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. This study aimed to develop ε-PLL@SA/Gel (PSG) hydrogels by incorporating varying concentrations of ε-poly-L-lysine (ε-PLL) into sodium alginate/gelatin (SA/Gel) using calcium chloride as a crosslinking agent, and to evaluate their antibacterial efficacy.

The mechanical properties, biocompatibility, antibacterial activity of hydrogels were evaluated. Biocompatibility was examined by measuring cell viability and proliferation of human skin fibroblasts in vitro. Antibacterial efficacy against Escherichia coli and Staphylococcus aureus was quantified using bacterial inhibition assays. The wound healing efficacy of the hydrogels were evaluated in mouse models of infected wounds.

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.

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.