Antibiotic‐Free Cationic Dendritic Hydrogels as Surgical‐Site‐Infection‐Inhibiting Coatings

• Published in: Advanced healthcare materials 2019-03, Vol.8 (5), p.e1801619-n/a
• Main Authors: Andrén, Oliver C. J., Ingverud, Tobias, Hult, Daniel, Håkansson, Joakim, Bogestål, Yalda, Caous, Josefin S., Blom, Kristina, Zhang, Yuning, Andersson, Therese, Pedersen, Emma, Björn, Camilla, Löwenhielm, Peter, Malkoch, Michael
• Format: Article
• Language: English
• Subjects: Alanine; Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; antibacterial; Antibiotics; Antiinfectives and antibacterials; Biocompatibility; Cartilage; Cartilage - drug effects; Cations - chemistry; dendrimer; Dendritic structure; Hydrogels; Hydrogels - chemistry; Hydrogels - pharmacology; Infections; Mechanical properties; Mice; Polyethylene glycol; Polyethylene Glycols - chemistry; Propionic acid; Surgical site infections; Surgical Wound Infection - drug therapy; surgical-site infection; Tissue Engineering - methods
• ISSN: 2192-2640; 2192-2659; 2192-2659
• DOI: 10.1002/adhm.201801619

A non‐toxic hydrolytically fast‐degradable antibacterial hydrogel is herein presented to preemptively treat surgical site infections during the first crucial 24 h period without relying on conventional antibiotics. The approach capitalizes on a two‐component system that form antibacterial hydrogels within 1 min and consist of i) an amine functional linear‐dendritic hybrid based on linear poly(ethylene glycol) and dendritic 2,2‐bis(hydroxymethyl)propionic acid, and ii) a di‐N‐hydroxysuccinimide functional poly(ethylene glycol) cross‐linker. Broad spectrum antibacterial effect is achieved by multivalent representation of catatonically charged β‐alanine on the dendritic periphery of the linear dendritic component. The hydrogels can be applied readily in an in vivo setting using a two‐component syringe delivery system and the mechanical properties can accurately be tuned in the range equivalent to fat tissue and cartilage (G′ = 0.5–8 kPa). The antibacterial effect is demonstrated both in vitro toward a range of relevant bacterial strains and in an in vivo mouse model of surgical site infection. Dendritic polymers in a formulation of antibacterial hydrogels are aimed to preemptively treat surgical site infections without relying on conventional anti‐biotics. Spontaneous gelation is observed within 1 min at physiological conditions with tunable moduli, in the range of tissue. Broad spectrum antibacterial effect is demonstrated both in vitro toward a range of relevant strains and in an in vivo mouse model.