Chitosan-coated cerium oxide nanocubes accelerate cutaneous wound healing by curtailing persistent inflammation

Inflammation is the initial phase in the healing of cutaneous wounds; however, persistent inflammation will hamper the healing process by generating excess inflammatory cytokines and reactive oxygen species (ROS). Therefore, preventing persistent inflammation and clearing redundant ROS are important strategies in accelerating wound healing. Owing to their unique redox activity, cerium oxide (CeO2) nanoparticles have shown promising potential as antioxidative and anti-inflammatory agents for the treatment of various diseases resulting from oxidative stress. In the present study, we prepared chitosan-coated CeO2 nanocubes (CCNs) and evaluated their cutaneous wound healing potential when topically applied to open excision wounds on adult Sprague Dawley (SD) rats. CCN application significantly increased the wound healing rates and showed superior wound healing capabilities compared to a clinically applied wound healing agent, recombinant human epidermal growth factor (rhEGF). We attribute this superior wound healing ability to their anti-inflammatory ability by decreasing the expression of the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) and increasing the expression of the anti-inflammatory cytokine interleukin-10 (IL-10), as well as to their antioxidative ability by increasing antioxidant enzyme levels. These results suggest that CCNs hold therapeutic potential in treating refractory wounds characterized by persistent inflammation caused by oxidative-stress related diseases such as diabetes.