Importance Of Oxidative Stress On The Initiation Of Chronic Wound Development In A Diabetic Chronic Wound Mouse Model
Jane H. Kim, Amanda Tedesco, Paul Ruegger, James Borneman, Manuela Martins-Green.
University of California, Riverside, Riverside, CA, USA.
Human chronic wounds have high levels oxidative stress (OS) but to date it is not known how OS contributes to initiation of chronicity. Most of the time well-controlled experiments cannot be performed in humans. However, animal models have proven very effective in understanding disease in humans. We have developed a model of chronic wounds in diabetic mice that mimic many of the aspects of human chronic wounds including biofilm developing naturally, i.e. without the introduction of external bacteria into the wound. To create the chronic wounds in this mouse model, we used inhibitors of anti-oxidant enzymes to increase levels of OS. We hypothesize that oxidative stress levels are critical for development of chronicity including biofilm formation. We used different concentrations of inhibitors of anti-oxidant enzymes to cause OS and found that the wounds healed better as the levels of inhibitors, used to induce OS, decreased. To further determine whether OS influences the quantity and quality of the microbiome, we collected the biofilm over time, analyzed it using bacterial intergenic transcribed spacer sequences and found differences in microbial composition of wounds that heal compared to wounds that remain chronic. To further determine the importance of OS in chronic wound development, we took biofilm from fully chronic wounds and applied it to new wounds without increasing OS. We found that in the absence of OS the biofilm alone was unable make the wounds chronic. Conversely, increasing OS in wounds, when keeping the wounds clean, delayed chronicity, suggesting that both high levels of OS and bacteria are needed for initiation of chronicity. In conclusion, we propose that level of OS in a wound may be a good predictor of degree of chronicity and that managing OS in chronic wounds after debridement could lead to wound closure and improved healing preventing return of chronicity.
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