Nature-Inspired Scarless Healing: Guiding Biomaterials Design for Advanced Therapies.

The use of biomaterials in the treatment of skin wounds has been steadily increasing over the last two decades. The key to the successful application of biomaterials in scar reduction is the up-to-date knowledge of the actors involved in accelerated healing and the cellular factors that can be implemented in bio-inspired materials. Natural models of scarless healing such as oral mucosa, foetal skin and the skin of amphibians, fish and reptiles are a great source of information. By investigating their microenvironments, cellular factors and inflammatory self-regulatory systems, a general model of scarless healing can be defined. This review introduces the basic and current concepts of skin wound healing and focuses on providing a detailed overview of the main processes of accelerated healing without scarring. The paper outlines the common features and key points that develop and promote scar-free healing. The tissues and healing processes of the selected natural models are described individually (tissue organisation, structural components, ratios of cellular factors such as Collagen and TGF and their mechanisms of regulation of inflammation and scar overgrowth). A comparative work of each natural model concerning healing in human skin is included in the discussion. Finally, the patterns identified through the analysis of each model and their differences from normal healing are presented to facilitate the knowledge for the implementation of new treatments.