Combined antimicrobial and pro-healing effects of cathelicidins in a polysaccharide-based hydrogel scaffold: treatment of carbapenemase-resistant Pseudomonas aeruginosa wound infections in a porcine model.

Given the global rise in antibiotic resistance, this study focuses on developing an alternative treatment for deep skin and soft tissue infections (SSTIs) caused by a carbapenem-resistant Pseudomonas aeruginosa. An injectable hydrogel composed of polyvinyl alcohol and chitosan was developed as a stable carrier for the porcine cathelicidins PR-39 and Protegrin-1. In vitro tests demonstrated that the addition of 8 mM EDTA fully restores the activity of antibacterial peptides in fetal bovine serum and eliminates the influence of divalent cations. In a porcine model, the application of this hydrogel resulted in a significant reduction in bacterial load after only two doses, with levels dropping below 105 CFU/g of tissue. In addition to eliminating the infection, the treated group showed early granulation tissue formation, reduced necrosis and inflammation, and the development of a continuous epidermis, all of which were completely absent in the untreated group. The research confirms that the combination of cathelicidins and EDTA in a hydrogel carrier represents a highly effective approach for treating complicated bacterial infections.