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Journal of Diabetes Research
Volume 2014 (2014), Article ID 562625, 18 pages
http://dx.doi.org/10.1155/2014/562625
Research Article

Generating and Reversing Chronic Wounds in Diabetic Mice by Manipulating Wound Redox Parameters

1Department of Cell Biology and Neuroscience, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USA
2Bioengineering Interdepartmental Graduate Program, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USA
3Division of Biomedical Sciences, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USA
4Department of Botany and Plant Sciences, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USA
5Department of Computer Science and Engineering, University of California, Riverside, Riverside, CA 92521, USA

Received 5 September 2014; Revised 18 November 2014; Accepted 18 November 2014; Published 23 December 2014

Academic Editor: Ronald G. Tilton

Copyright © 2014 Sandeep Dhall et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

By 2025, more than 500 M people worldwide will suffer from diabetes; 125 M will develop foot ulcer(s) and 20 M will undergo an amputation, creating a major health problem. Understanding how these wounds become chronic will provide insights to reverse chronicity. We hypothesized that oxidative stress (OS) in wounds is a critical component for generation of chronicity. We used the db/db mouse model of impaired healing and inhibited, at time of injury, two major antioxidant enzymes, catalase and glutathione peroxidase, creating high OS in the wounds. This was necessary and sufficient to trigger wounds to become chronic. The wounds initially contained a polymicrobial community that with time selected for specific biofilm-forming bacteria. To reverse chronicity we treated the wounds with the antioxidants α-tocopherol and N-acetylcysteine and found that OS was highly reduced, biofilms had increased sensitivity to antibiotics, and granulation tissue was formed with proper collagen deposition and remodeling. We show for the first time generation of chronic wounds in which biofilm develops spontaneously, illustrating importance of early and continued redox imbalance coupled with the presence of biofilm in development of wound chronicity. This model will help decipher additional mechanisms and potentially better diagnosis of chronicity and treatment of human chronic wounds.