An injectable hydrogel wound dressing based on an oxidized dextran and ε-poly-l-lysine network has multiple biological activities.

Open wounds (e.g., burns and trauma) are always challenged by various opportunistic bacteria. There is an urgent need for developing novel wound dressing that is able to prevent bacterial infection and promote the healing simultaneously. Herein, we developed a new type of antimicrobial hydrogels for the open wound healing through imitating a facile mussel-inspired catechol/polyamine chemistry. This hydrogel was prepared using catechol (CT) and ε-poly-L-lysine (EPL) by oxidative cross-linking directly in the open air at room temperature. This nonleaching CT/EPL hydrogel not only exhibited excellent contact-active antimicrobial activities against Gram-negative bacteria Escherichia coli (E. coli) and Gram-positive "superbug" methicillin-resistant Staphylococcus aureus (MRSA) but also inhibited the biofilm formation in vitro. Moreover, the animal burn wound model study clearly validated the in vivo anti-infective property of CT/EPL hydrogel against MRSA infection. More importantly, the CT/EPL hydrogel possessed low cytotoxicity and enhanced cell migration in vitro. A full-thickness cutaneous wound model study revealed that CT/EPL hydrogel upregulated the expression of vascular endothelial growth factor (VEGF) and reduced the production of the pro-inflammatory cytokines, thus promoted the wound healing. These findings suggested that the CT/EPL hydrogel have great potential as a wound dressing for preventing bacterial infection and accelerating healing of open wounds.

Despite the excellent antimicrobial activity, the high toxicity and low selectivity of cationic antimicrobial peptides (AMPs) and their synthetic analogues impede their biomedical applications. In this study, we report a series of cationic peptidopolysaccharides synthesized by thiol−ene click chemistry of grafting antimicrobial polypeptides, methacrylate-ended poly(lysine-random-phenylalanine) (Me-K n F m ), onto a thiolated polysaccharide (dextran, Dex) backbone. Their copolymers (Dex-g-K n F m ) exhibit potent broad-spectrum antibacterial and antifungal activity against Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli), Gram-positive bacteria [methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis], and fungi (Candida albicans) with minimal inhibitory concentrations in the range of 31.25−500 μg•mL −1 . More importantly, Dex-g-K n F m copolymers did not induce drug resistance of MRSA up to 17 passages. In addition, these copolymers have an improved hemocompatibility and exhibit good in vitro biocompatibility with murine myoblast (C2C12) cells. Among the synthesized peptidopolysaccharides, Dex L -g-K 12.5 F 12.5 -50%, as the optimal agent, displayed a selectivity more than 200 times the maximum value of polypeptide molecules. Furthermore, a strong in vivo antimicrobial efficacy with a log reduction above 3 in a mouse bacterial sepsis model has been obtained. These excellent biological properties present a promising prospect for Dexg-K n F m in biomedical applications.