Hydrazone-crosslinked poly(oligoethylene glycol methacrylate)-based hydrogels with physically entrapped phage effectively control Pseudomonas aeruginosa infections in a burn wound model

Abstract:

First-line treatments for treating wound infections are under threat from the increase in antimicrobial resistant bacteria, a threat further exacerbated in burn wounds in which the immune response to the infection site is blocked by burned skin. Herein, we report a tuneable and in situ-gelling poly(oligoethylene glycol methacrylate) bulk hydrogel containing bacteriophage (phage), viruses that allow for highly efficient and specific killing of bacteria without the need for conventional antibiotics. The resulting phage-hydrogel has suitable mechanical strength (1.5 kPa compressive modulus) and stability (up to 5 days when fully hydrated) for use as a burn wound dressing while also maintaining excellent antibiotic properties (>4-log reduction of Pseudomonas aeruginosa in a murine in vivo infection burn wound model). Coupled with the beneficial hydrating properties of hydrogels for promoting burn wound healing, the phage-hydrogel dressing offers potential for managing complex burn wound infections.

Hydrogel rheology

Rheological testing was performed using a Mach-1 Mechanical Tester (Biomomentum Inc., Laval QC). A parallel plate geometry was used with an indenter diameter of 12.7 mm. Hydrogels were allowed to equilibrate at room temperature overnight prior to testing at room temperature. The compressive modulus was measured by compressing the gels to 80 % of their original height at a rate 1 %/s. The shear storage modulus was measured by first performing a strain sweep test from 0.1 to 2.2° at 0.5 Hz to identify the linear viscoelastic region followed by a frequency sweep test from 0.1 to 2.2 Hz within the linear viscoelastic region. All tests were performed with 4 replicates, with the error bars representing standard deviation.

Keywords:

Hydrogel; Burn wound; Infection; Bacteriophage.