The quest for the perfect healing of human skin wounds: Promising models

Human skin is a compound organ performing essential functions in direct environmental contact. An orchestrated set of complex biological processes sustained by intricate molecular interactions leads to skin wound healing. Only superficial (epidermal) lesions heal perfectly (i.e., without scars). Intermediate or deep and extended skin (burn) wounds prevent the status quo ante restoration , resulting in hypertrophic/retracting scars or keloids, often entailing ugly sequels. Thus, a quest, punctuated by innumerable approaches, has been and is on to achieve a (nearly) perfect healing. This work focuses on various models, such as the Mexican axolotl and the spiny mouse, two distinct types of pig split-skin dressings, and acellular 3D silk fibroin nonwoven scaffold implants, in which examples of perfect skin regenesis/regeneration occurred. It also discusses novel reconstituted acellular biomaterial scaffolds, including dermal matrisome components because of their skin regeneration-promoting qualities. An analysis of the available evidence shows that the matrisome components of the dermis and hypodermis in specific embryo, fetal, and newborn vertebrates contribute to perfect skin wound healing. Some of these components have yet to be identified. It is mandatory to clarify the specific role(s) of each matrisomal constituent cooperating in the wound repair mechanisms. These studies will advance the development of novel therapeutic strategies promoting scar-free or so skin wound healing, thus restoring the original morpho-functional characteristics.