Abstract
SIGNIFICANCE: The skin is our largest organ, with the primary role of protection against assaults from the outside world. It also suffers frequent damage, from minor scrapes to, more rarely, complete destruction such as in third-degree burns. It is therefore, by its nature, an organ that would benefit tremendously from being able to regenerate itself. RECENT ADVANCES: This review highlights the axolotl, a less well-known model organism capable of scarless wound healing and regeneration. Axolotls are salamanders with unsurpassed healing and regenerative capacities. Understanding how these animals can regenerate their tissues could help identify the pathways that need to be activated or inhibited in humans to improve wound healing. CRITICAL ISSUES: Presently, there are no therapies leading to skin regeneration or scarless wound healing. Various animal models have thus been developed for use in research, such as mice and pigs, to help us understand how wound healing could be improved or stimulated. However, these more common models cannot regenerate and, consequently, cannot direct us toward a solution to regenerate damaged tissues. Axolotls, on the other hand, can regenerate perfectly and therefore may offer avenues to identify molecular targets for therapeutic intervention. FUTURE DIRECTIONS: Identifying signaling pathways regulating tissue regeneration in vertebrate models is important. The use of animals such as axolotls, which hold the secret of full regeneration, will likely play a significant role in helping us achieve scarless wound healing for humans.