Cu-MOF loaded chitosan based freeze-dried highly porous dressings with anti-biofilm and pro-angiogenic activities accelerated Pseudomonas aeruginosa infected wounds healing in rats

Abstract

Metal–organic frameworks (MOFs)-based therapy opens a new area for antibiotic-drug free infections treatment. In the present study, chitosan membranes (CS) loaded with two concentrations of copper-MOF 10 mg/20 ml (Cu-MOF10/CS) & 20 mg/20 ml (Cu-MOF20/CS) were prepared by a simple lyophilization procedure. FTIR spectra of Cu-MOF10/CS and Cu-MOF20/CS dressings confirmed absence of any undesirable chemical changes after loading Cu-MOF. The SEM images of the synthesized materials (CS, Cu-MOF10/CS & Cu-MOF20/CS) showed interconnected porous structures. Cytocompatibility of the materials was confirmed by fibroblasts cells culturing and the materials were hemocompatible, with blood clotting index <5 %. Cu-MOF20/CS showed comparatively higher effective antibacterial activity against the tested strains; E. coli (149.2 %), P. aeruginosa (165 %) S. aureus (117.8 %) and MRSA (142 %) as compared to Amikacin, CS and Cu-MOF10/CS membranes. Similarly, Cu-MOF20/CS dressing significantly eradicated the biofilms; P. aeruginosa (37 %) and MRSA (52 %) respectively. In full thickness infected wound rat model, on day 23, Cu-MOF10/CS and Cu-MOF20/CS promoted wound healing up to 87.7 % and 82 % respectively. H&E staining of wounded tissues treated with Cu-MOF10/CS & Cu-MOF20/CS demonstrated enhanced neovascularization and re-epithelization along-with reduced inflammation, while trichrome staining exhibited increased collagen deposition. Overall, this study declares Cu-MOFs loaded chitosan dressings a multifunctional platform for the healing of infected wounds.