Protocol to Create Chronic Wounds in Diabetic Mice - an Update to the Published Protocol
Jane Hannah Kim1, Parnian Jabbari1, Manuela Martins-Green2
1Department of Molecular, Cell, and Systems Biology, University of California, Riverside.
Abstract:
Despite considerable efforts to treat chronic wounds, success has been limited. The cellular and molecular processes that disrupt normal healing and contribute to the initiation and development of chronic wounds are not well understood. As a result, developing effective treatments for these wounds has proven challenging. This is primarily because of the lack of animal models that mimic chronic wounds in humans and because experimentation in humans with chronic wounds is limited. Previously, we have published a mouse model to study chronic wounds that share many characteristics with diabetic chronic wounds in humans. This model includes the presence of biofilms formed naturally from bacteria found in skin microbiota and the environment without the need to introduce external bacteria into the wounds. Therefore, this model can potentially advance the fundamental understanding of how wounds become chronic. Here, we present an update to the original protocol for developing this mouse model. We have concentrated on decreasing the mortality of mice from ~30% to ~5%. We also describe how this model has been used to understand the initiation and progression of wound chronicity by using next-generation transcriptomic approaches, elucidating bacterial population dynamics during infection and biofilm development, and demonstrating the value of testing the efficacy of treatments, including small molecules. So far, this is the only chronic wound model that does not heal without intervention.
Insights
This study refines a chronic wound mouse model, improving survival rates and enabling deeper understanding of wound healing. The model mimics human diabetic wounds, aiding research into chronic wound development and treatment efficacy.
Area of Science:
- Wound Healing Research
- Animal Models of Disease
- Microbiology and Infectious Diseases
Background:
- Chronic wound treatment remains challenging due to poorly understood healing disruptions.
- Existing animal models inadequately replicate human chronic wound conditions.
- A previously developed mouse model mimics human diabetic chronic wounds, including natural biofilm formation.
Purpose of the Study:
- To present an updated protocol for a chronic wound mouse model with reduced mortality.
- To detail the application of this model in understanding wound chronicity using advanced techniques.
- To demonstrate the model's utility in evaluating treatment efficacy.
Main Methods:
- Refinement of an existing mouse model for chronic wound research.
- Implementation of next-generation transcriptomic analyses for cellular and molecular insights.
- Investigation of bacterial dynamics, including infection and biofilm development.
- Assessment of treatment efficacy, including small molecule interventions.
Main Results:
- Mortality in the mouse model significantly reduced from approximately 30% to 5%.
- The model facilitates the study of wound chronicity initiation and progression.
- Transcriptomic and bacterial analyses provide insights into chronic wound pathophysiology.
- The model is validated as the only existing chronic wound model that fails to heal without intervention.
Conclusions:
- The updated mouse model offers a more viable and informative platform for chronic wound research.
- This model advances the understanding of the cellular, molecular, and microbial factors in chronic wound development.
- It serves as a crucial tool for preclinical testing of novel therapeutic strategies for non-healing wounds.
