Protocol to Create Chronic Wounds in Diabetic Mice
Jane Hannah Kim1, Manuela Martins-Green2
1Department of Molecular, Cell and Systems Biology, University of California, Riverside.
Abstract:
Chronic wounds develop as a result of defective regulation in one or more complex cellular and molecular processes involved in proper healing. They impact ~6.5M people and cost ~$40B/year in the US alone. Although a significant effort has been invested in understanding how chronic wounds develop in humans, fundamental questions remain unanswered. Recently, we developed a novel mouse model for diabetic chronic wounds that have many characteristics of human chronic wounds. Using db/db-/- mice, we can generate chronic wounds by inducing high levels of oxidative stress (OS) in the wound tissue immediately after wounding, using a one-time treatment with inhibitors specific to the antioxidant enzymes catalase and glutathione peroxidase. These wounds have high levels of OS, develop biofilm naturally, become fully chronic within 20 days after treatment and can remain open more for more than 60 days. This novel model has many features of diabetic chronic wounds in humans and therefore can contribute significantly to advancing fundamental understanding of how wounds become chronic. This is a major breakthrough because chronic wounds in humans cause significant pain and distress to patients and result in amputation if unresolved. Moreover, these wounds are very expensive and time-consuming to treat, and lead to significant loss of personal income to patients. Advancements in this field of study through the use of our chronic wound model can significantly improve health care for millions who suffer under this debilitating condition. In this protocol, we describe in great detail the procedure to cause acute wounds to become chronic, which has not been done before.
Insights
Researchers developed a new mouse model for diabetic chronic wounds. This model mimics human chronic wounds, aiding research into healing defects and improving patient care.
Area of Science:
- Biomedical Science
- Wound Healing Research
- Animal Models
Background:
- Chronic wounds affect millions, incurring significant healthcare costs.
- Defective regulation of cellular and molecular processes underlies chronic wound development.
- Existing research has not fully elucidated the mechanisms of chronic wound formation.
Purpose of the Study:
- To introduce a novel mouse model for studying diabetic chronic wounds.
- To provide a reproducible method for generating chronic wounds in a preclinical setting.
- To facilitate a deeper understanding of the pathophysiology of chronic wound development.
Main Methods:
- Utilized db/db-/- mice to create a diabetic chronic wound model.
- Induced high levels of oxidative stress (OS) post-wounding using specific antioxidant enzyme inhibitors (catalase and glutathione peroxidase).
- Characterized the resulting wounds for OS levels, biofilm formation, and chronicity duration.
Main Results:
- The developed model exhibits key characteristics of human diabetic chronic wounds.
- Wounds demonstrated elevated OS, natural biofilm development, and became chronic within 20 days.
- Wounds remained open for over 60 days, indicating a persistent chronic state.
Conclusions:
- This novel mouse model offers a significant advancement for chronic wound research.
- The model's fidelity to human chronic wounds can accelerate the understanding of healing defects.
- Findings from this model hold potential to improve therapeutic strategies and patient outcomes for chronic wounds.
