Application of three-dimensional bacteriophage cocktail biogel on infected burn wounds in rats.

Abstract

Burn wound infections significantly hinder the healing process by disrupting the immune response and limiting treatment options due to increasing antibiotic resistance. In this study, the antimicrobial and tissue regeneration effects of a three-dimensional bacteriophage cocktail bio-gel were evaluated in vivo in burn wounds infected with antibiotic-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. Using an experimental burn model in Sprague Dawley rats, the effects of phage bio-gel treatment on inflammatory response, cellular repair mechanisms, and wound closure dynamics were analyzed through molecular, biochemical, and histopathological assessments. Application of the bacteriophage bio-gel significantly accelerated wound healing in infected burn groups, with healing rates ranging from 77.56 to 89.75% on days 15 and 20. Cytokine analysis demonstrated that phage therapy modulated inflammation by reducing IL-1β, IL-6, and TNF-α levels (p < 0.05). Molecular analyses examining extracellular matrix dynamics showed a significant increase in TGF-β1, Smad-2/3, and collagen type 1 gene expression, indicating enhanced fibroblast activation and tissue remodeling. While MMP-2 and hydroxyproline levels increased, MMP-9 levels decreased following phage treatment. Histopathological evaluations revealed that re-epithelialization and tissue remodeling were accelerated, while inflammation was reduced in the A. baumannii and K. pneumoniae infected groups. These findings suggest that bacteriophage-based bio-gels provide a promising alternative for treating polymicrobial burn wound infections. The results indicate that bacteriophage biomaterials exhibit superior wound healing potential compared to conventional treatments, particularly in infections caused by antibiotic-resistant pathogens.