A multifunctional shape-adaptive and biodegradable hydrogel with hemorrhage control and broad-spectrum antimicrobial activity for wound healing

Abstract

Hemorrhage is the leading cause of preventable death of injured military and civilian patients, and subsequent infection risks endanger their lives or impede the healing of their wounds. Here, we report an injectable biodegradable hydrogel with hemostatic, antimicrobial, and healing-promoting properties. The hydrogel was prepared by dynamic cross-linking of a natural polysaccharide (dextran) with antimicrobial peptide ε-poly-L-lysine (EPL) and encapsulating base fibroblast growth factor (bFGF). The amino groups of EPL were allowed to react with the aldehyde of oxidized dextran (OD) through the Schiff-base reaction for the generation of hydrogels that have fast self-healing and injectable characteristics and adapt to the shapes of wounds. The prepared OD/EPL hydrogels promoted blood clotting in vitro and stopped bleeding in a rat liver injury model within 6 min through their platelet-aggregating ability and sealing effect. These hydrogels exhibited inherent antimicrobial effects without the use of antibiotics and effectively killed a broad spectrum of pathogenic microbes, including Gram-positive methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative Escherichia coli, and Pseudomonas aeruginosa and fungus Candida albicans in vitro. Moreover, these OD/EPL hydrogels were compatible with mammalian cells in vitro and in vivo and biodegradable in the mouse body. The loaded bFGF can be released sustainably, and it can promote angiogenesis, endothelial cell migration, and consequently accelerate the healing of wounds. The OD/EPL hydrogel inhibited MRSA infection in a rat full-thickness skin wound model and promoted healing. This kind of multifunctional hydrogel is a promising wound dressing for the emergency treatment of acute deep or penetrating injuries.