A new study reports on unique antibiotic-free hydrogels that induce immune modulation in human keratinocytes, providing an effective solution against a broad spectrum of bacteria.

Developed at KTH Royal Institute of Technology (KTH; Stockholm, Sweden), Karolinska Institutet (Solna, Sweden), and other institutions, the new H10K-G5 cationic hydrogel is based on hyperbranched dendritic–linear–dendritic copolymers (HBDLDs). Resembling trees, the dendritic polymers' branches terminate with numerous peripheral contact points carrying a cationic charge which interact strongly with negatively-charged bacterial cell membranes. The hydrogels are formed spontaneously when sprayed on wounds, and are 100% degradable and non-toxic.

In the study, H10K-G5 exhibited excellent antimicrobial activity to a wide range of clinical Gram-positive and Gram-negative bacteria, including drug-resistant strains isolated from wounds. H10K-G5 works by inducing expression of the antimicrobial peptides RNase 7 and psoriasin, promoting host-mediated bacterial killing in human keratinocytes. It also decreases pro-inflammatory cytokine IL-1β, reactive nitrogen species, and mitochondrial reactive oxygen species (ROS) in S. aureus-infected keratinocytes, conjunctively resulting in reduced inflammation. The study was published on October 12, 2021, in Journal of the American Chemical Society (JACS).

“Bacterial cells are interactive, and so are dendritic macromolecules. When they meet, it doesn't turn out well for the bacteria,” said co-senior author Professor Annelie Brauner, PhD, of Karolinska Institutet. “Contrary to traditional antibiotics, resistance towards antimicrobial peptides is very rarely seen. The gel is an outstanding contribution in the fight against multidrug-resistant bacteria, especially in current times, when we are running out of available antibiotics.”

Infections caused by antibiotic-resistant bacteria are a major global threat, leading to high mortality rates and increased economic burden. Novel treatment strategies are therefore urgently needed by healthcare providers. Biomaterials such as HBDLDs, which are based on polyethylene glycol (PEG) and propionic acid (bis-MPA), with inherent antibacterial properties, which do not require the use of antibiotics, present an attractive and feasible avenue to achieve this goal. 

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