Comparative Analysis of Animal Models in Wound Healing Research and the Utility for Humanized Mice Models.

Significance: The rise of chronic nonhealing lower extremity wounds among aging, diabetic, obese, and cardiovascular patients has surged. Despite a decade of drug testing in preclinical animal models, few federally approved therapies have emerged. This translational gap raises concerns about the efficacy of current wound healing models and the need for improved research development. Recent Advances: To improve commonly used animal models of chronic wounds, researchers have made several animal model modifications to better mimic and understand the microbiota and immune-mediated wound healing processes that occur in humans. Critical Issues: Existing models do not fully account for the differences in skin architecture, healing processes, and immune system responses in wound healing between animal models and humans. Therefore, it is imperative to understand the limitations of a chosen model when designing experiments. As such, findings must be interpreted cautiously and validated in human contexts. Future Directions: Given the complexity of human wound healing, the use of several different animal models tailored to specific biological questions is necessary. Recent advancement in humanized mouse models and microbiota consideration offer a promising approach to study the human immune-mediated response in chronic wound healing.