Gel fights drug-resistant bacteria and induces body’s natural immune defense

In the fight against multidrug-resistant bacteria, scientists in Sweden have developed a new kind of antibiotic-free protection for wounds that kills drug-resistant bacteria and induces the body’s own immune responses to fight infections.

Reporting in Journal of the American Chemical Society, researchers from KTH Royal Institute of Technology, Karolinska Institutet and Karolinska University Hospital say that the new treatment is based on specially-developed hydrogels consisting of polymers known as dendritic macromolecules. The hydrogels are formed spontaneously when sprayed on wounds and 100 percent degradable and non-toxic.

Karolinska Institutet Professor Annelie Brauner says that despite containing no antibiotics, the hydrogels show excellent antibacterial qualities and were effective against a broad spectrum of clinical bacteria, killing both Gram-positive and Gram-negative bacteria, including drug-resistant strains isolated from wounds. The material also reduces inflammation, according to the researchers.

The hydrogels were tested against several clinically relevant infectious bacteria, including Staphylococcus aureus (S. aureus), and Pseudomonas aeruginosa (P. aeruginosa). The hydrogels were shown to be 100 percent effective in killing P. aeruginosa; and almost equally effective in killing S. aureus.

Cell infection tests demonstrated that the gel not only efficiently killed clinical drug-resistant bacteria from wounds, but also induced the expression of naturally-existing antimicrobial peptides-or endogenous antibiotics-in human skin cells.

Stimulated endogenous antibiotics

Professor Annelie Brauner at Karolinska Institutet.
Photo: Fredrik Persson

“These endogenous antibiotics help fight bacteria and clear the infection,” says Annelie Brauner who is at the Department of Microbiology, Tumor and Cell Biology and joint corresponding author. “Contrary to traditional antibiotics, where bacteria may develop resistance quickly, resistance towards antimicrobial peptides, is very rarely seen.”

The hydrogel was also more successful in killing methicillin-resistant S. aureus (MRSA) when compared to a commercially available hydrogel wound dressing in use today.

“Dendritic hydrogels are excellent for wound dressing materials because of their soft, adhesive and pliable tactile properties, which provide ideal contact on the skin and maintain the moist environment beneficial for optimal wound healing,” says KTH Professor Michael Malkoch, who is also joint corresponding author.

The antibacterial effects of the hydrogels have yet to be fully understood, but the key lies in these macromolecules’ structure. It’s distinguished by well-ordered branches that terminate with a profusion of cationic, charged contact points.

Ideal scaffolds for biomedical applications

Michael Malkock

Professor Michael Malkock at KTH Royal Institute of Technology.
Photo: KTH

“Bacterial cells are interactive, and so are dendritic macromolecules,” Michael Malkoch says. “When they meet, it doesn’t turn out well for the bacteria.”

The dendritic polymers that comprise the hydrogel are based on polyethylene glycol (PEG) and propionic acid (bis-MPA). Resembling beautifully pruned apple trees, dendritic polymers’ branches terminate with numerous peripheral contact points carrying a cationic charge which interact strongly with negatively-charged bacterial cell membranes.

“Their well-designed, branched structure and scalability makes them ideal scaffolds for biomedical applications,” Michael Malkoch says.

Malkoch’s lab has been targeting skin infections with the dendritic-based platform for more than a year, and the new publication reports that the synthesis for the hydrogels is less complicated and easily scalable.

“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,” Annelie Brauner says.

This news article is based on a press release from KTH Royal Institute of Technology.

Publication

Dendritic hydrogels induce immune modulation in human keratinocytes and effectively eradicate bacterial pathogens.” Yanmiao Fan§a, Soumitra Mohanty§b, Yuning Zhang, Mads Lüchow, Liguo Qin, Lisa Fortuin, Annelie Brauner*b and Michael Malkoch*a, Journal of the American Chemical Society, online Oct. 12, 2021, doi: 10.1012/jacs.1c07492

§ Joint first authors, * Joint last authors

a KTH b KI

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