Validation of safety and efficacy of the antimicrobial hydrogel for rapid elimination of bacterial infection in murine and porcine infected wounds

Summary: Abstract Body: Our study focused on development of a targeted antibacterial pH/temperature responsive silver nanoparticle (AgNP) hydrogel allowing triggered release of silver ions in response to changes in wound microenvironment. Optimization and characterization of the hydrogel delivery system was achieved using cross-linking of N-isopropylacrylamide with acrylic acid and loading with ultrasmall AgNPs. Material characterization, biocompatibility and release studies were undertaken to demonstrate temperature and pH responsive properties and in-vitro efficacy against common wound pathogens. Demonstration of in-vivo antimicrobial safety and efficacy against industry standard of care (silver sulfadiazine) was achieved using a preclinical murine and porcine wound infection models. We demonstrate that the dual-responsive hydrogel is highly sensitive to a typical pH and temperature changes during infection development, with restricted release of silver ions at acidic pH (pH 7.4) (>90% release). The pH dependent release and antimicrobial effect resulted in elimination of 95% of pathogens in-vitro at alkaline pH which was confirmed by potent clearing of S. aureus infection and significant improved healing using preclinical models including faster reepithelization and improved early collagen deposition. Treatment safety were further validated in porcine model of wound infection, with developed hydrogel showing no toxicity and equivalent antimicrobial effects to industry standard of care. This multifunctional hydrogel presents a promising bacteria responsive delivery platform that serves as an on-demand carrier to not only reduce side effects but also boost the antibacterial efficiency based on physiological needs. It offers great potential to improve the way we manage wound infections, providing a single platform for a long-lasting application in wound management. Anna Antipov¹, Tahlia Kennewell¹, Adrian Abdo², Hanif Haidari¹, Zlatko Kopecki¹ 1. Wound Infection Laboratory, University of South Australia Future Industries Institute, Adelaide, SA, Australia. 2. University of Adelaide, Basel Hetzel Institute, Adelaide, SA, Australia. Translational Studies: Preclinical