Antibacterial Hydrogels to Treat Burn Wound Infections

Abstract

The increasing prevalence of antibiotic-resistant bacteria in healthcare settings is threatening conventional methods of infection control and prevention. Certain injuries, like burns in which the immune response to the infection site is blocked by burned skin, are exceptionally vulnerable as host defences are additionally impaired. A hydrogel that utilizes alternative antimicrobials to resolve an infection would address both the threat of antibiotic-resistance and promote healing. This research demonstrates the utilization of in situ-gelling poly(oligoethylene glycol methacrylate) as a hydrogel system to deliver both conventional and alternative antibiotics. This was achieved through four aims: (1) to develop an infected burn wound mouse model, (2) to tether antibiotics and inherently antibacterial functional groups (quaternary ammonias) to the POEGMA-hydrogel system copolymer backbone, (3) to use POEGMA-based dynamic covalent hydrogels as a wound dressing to deliver phage to treat infected burn wounds, and (4) to fabricate an electrospun POEGMA hydrogel to deliver phage. The burn wound infection model was found to reliably develop an infection, thereby providing a platform upon which subsequent hydrogels could be tested. The quaternary-ammonium and ciprofloxacin-tethered hydrogel effectively reduced a Pseudomonas aeruginosa infection both in vitro and in vivo using the mouse burn wound infection model. Even tethered onto the polymer backbone, the antibiotic agents showed synergy. Delivering phage using the hydrogel platform resulted in an effective reduction of P. aeruginosa infection using the burn wound model, with phage entrapped in the hydrogel continuously released over the course of five days at pH levels reflective of normal skin pH and the slightly acidic environment of infected tissues. When electrospun into hydrogel-based nanofibres, the phage did not impact nanofibre morphology and remained infectious for up to 14 days when stored under refrigeration. Taken together, hydrogels developed herein have the potential to address AMR burn wound infections while also improving healing.