Scalable Dendritic Hydrogels Targeting Drug-Resistant Skin Pathogens and the Immunomodulation Activity in Keratinocytes

• Microbial infections caused by antibiotic-resistant bacteria are a major threat to humans, associated with a high mortality and for the society increased economic burden. To address this, a series of cationic hydrogels based on amino-functional hyperbranched dendritic−linear−dendritic copolymers (HBDLDs) were formed easily within 1 min through interactions between the amino-terminated HBDLDs and di(N-hydroxysuccinimide ester) functionalized polyethylene glycol (PEG). The hydrogels exhibited excellent inherent antimicrobial activity towards a wide range of Gram-positive and Gram-negative clinical bacteria including drug-resistant strains, isolated from wounds. In vitro cell infection assays showed that the hydrogels were able to significantly reduce cell infections caused by different strains, with the highest killing efficacy of 96% towards S. aureus. The hydrogels also inhibited the initiation of E. coli biofilm formation. Remarkably, the hydrogels induced the expression of the antimicrobial peptides, RNase 7 and psoriasin, in keratinocytes (HaCaT) which suggests that the hydrogels are likely able to promote host-mediated bacterial killing. The expression of pro-inflammatory cytokine IL-1β, reactive nitrogen species (NO) and mitochondrial reactive oxygen species (ROS) in S. aureus-infected HaCaT cells were reduced after the treatment with the hydrogels. The hydrogels degraded within 24 h, showing great promise for treating skin infections and reducing inflammation.

Keyword

cationic dendritic hydrogels

antimicrobial

drug-resistant bacteria

wound dressing

Publication and Content Type

vet (subject category)

ovr (subject category)