Key points for translating wound regenerative agents from in vivo assays in mice to clinical validation

Abstract

Skin wound healing leads to the recovery of tissue structure and homeostasis after injury. Numerous factors can hamper wound healing and complete recovery of the harmed tissue, causing the formation of scars or chronic wounds. Therapeutic options to improve wound regeneration are limited, possibly due to failure during pre-clinical validation toward clinical trials. In this article, the authors aim to convey key points and provide recommendations for the development of regenerative agents that improve wound healing using mouse models.First, the authors highlight the differences in the wound healing processes of mice and humans. Later, the authors apply a quasi-systematic research approach based on a search algorithm of 32 terms that focuses on in vivomouse model assays of regenerative factors. The authors analyze the top 20 most cited articles of 2241 hits produced by Scopus. The authors focus the search on a period covering the last 10 years (January 2011 to October 2021). The authors synthesize information from the top 20 articles and present the most common type of mouse model used, mouse characteristics (strain, sex, age, weight), surgical wounding technique employed (size, location, equipment), agents tested, methods of wound monitoring, regeneration assessment and key points to consider for the translational potential of these agents. This knowledge will help the scientific community design better in vivo assays and translate their results to further research and clinical validation.

Keywords: humanized mouse models; literature review; regeneration; repair; skin; wound healing agents.