| Summary: | Chronic skin wound is a chronic illness that possesses a risk of infection and sepsis. In particular, infections associated with antibiotic-resistant bacterial strains are challenging to treat. To combat this challenge, a suitable alternative that is complementary to antibiotics is desired for wound healing. In this work, we report multi-functional nanoscale chitosan vesicles loaded with manganese (Chi-Mn) that has potential to serve as a new tool to augment traditional antibiotic treatment for skin wound healing. Chi-Mn showed antioxidant activity increase over time as well as antimicrobial activity against <i>E. coli</i> and <i>P. aeruginosa</i> PA01. The modified motility assay that mimicked a skin wound before bacterial colonization showed inhibition of bacterial growth with Chi-Mn treatment at a low area density of 0.04 µg of Mn per cm<sup>2</sup>. Furthermore, this study demonstrated the compatibility of Chi-Mn with a commercial antibiotic showing no loss of antimicrobial potency. In vitro cytotoxicity of Chi-Mn was assessed with macrophages and dermal cell lines (J774A.1 and HDF) elucidating biocompatibility at a wide range (2 ppm–256 ppm). A scratch wound assay involving human dermal fibroblast (HDF) cells was performed to assess any negative effect of Chi-Mn on cell migration. Confocal microscopy study confirmed that Chi-Mn tested at the MIC (16 ppm Mn) has no effect on cell migration with respect to control. Overall, this study demonstrated the potential of Chi-Mn nanovesicles for wound healing applications.
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