Protocol to Create Chronic Wounds in Diabetic Mice - an Update to the Published Protocol.

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.