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

• PR-39, Protegrin-1, and EDTA combination display rapid antimicrobial activity. • EDTA restores activity of PR-39 and Protegrin-1 in fetal bovine serum. • PR-39 and Protegrin-1 act in synergy with chitosan and EDTA. • No formulation-related adverse effects were observed during the study. • The PVA/chitosan hydrogel is an effective delivery system for the therapy of SSTI. 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 10 5 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.