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HEALING SUPERPOWER: HOW FAR ARE WE FROM SCAR-FREE?



If you are a Spider-Man fan, you will probably be familiar with Dr. Curt Connors aka “The Lizard” and its super healing power, the ability to grow back an arm within seconds. Have you ever wondered “Can humans apply that super healing power for scar-free wound healing?”. Skin scarring is an inevitable consequence of injury, trauma, or even acne for humans. In the previous article, we already talk about scars’ formation and different scar types. Today’s article is focusing the future of scar-free healing.’


What is Regenerative Healing?

Tail regeneration of lizard


Regenerative healing refers to the ability of organisms to regenerate damaged tissues after injury, resulting in complete restoration of the original composite tissue architecture[1]. In adult mammals, healing typically results in the formation of a scar and damaged tissues cannot be regenerated, except in certain sites such as the liver, bone, and mucosal tissues [2]. However, lower organisms have the ability to regenerate tissues after injury, a process known as regenerative healing[1–3]. It is interesting to note that scarless healing can occur in early gestation of mammalian embryos, but this ability is lost as the postnatal period approaches, particularly in late gestation in humans where it occurs up to the last trimester of pregnancy [2].


The mechanism of scarless healing


The process of scarless healing is not yet fully understood, as the precise mechanisms that regulate regeneration and scarless healing remain unclear [4]. However, studies have identified significant differences between mammalian fetal and adult wound healing, including minimal inflammatory response, as well as differences in extracellular matrix (ECM) composition and modification such as collagen, tenascin, fibronectin, and hyaluronic acid [5, 6]. It has been demonstrated that the fetal environment is not the primary determinant of scarless healing, but rather the fetal tissue itself plays a crucial role [2]. Another striking difference between scar-free and scar-forming skin is the integrity and the abundance of blood vessels present within the wound bed [6]. Timing also appears to be a key factor in scarless healing, as starting the healing process as early as possible can decrease the likelihood of scar formation [1].


A future of scar-free healing


Although many advances have been made in the treatment of skin wounds, including different types of wound dressings, cell-based strategies, growth factors, and vacuum-assisted treatment, until now, none of them can support scarless wound healing in adult skin [4].

In the future, achieving scar-free healing may be possible with a comprehensive understanding of the mechanisms that regulate the transition from regeneration to scar formation. Newer strategies that combine pro-regenerative materials with optimal mechanical properties, suitable cell types, and soluble molecules offer a promising direction for tissue regeneration instead of simply repairing skin injury[5]. In combination with multi-target modulation therapy to enhance regenerative power and reduce harmful side effects [4].


Regeneration of wound and Scar formation [5]


References:

1. Noeline Subramaniam Kathy Jacyniak Rebecca McDonald Matthew K Vickaryous Young Reviewers Noah, A.P.: Lessons From Lizards: How Scaly Superhealers Can Help Humans. (2021). https://doi.org/10.3389/frym.2021.606902#:~:text=Some

2. Ud-Din, S., Volk, S.W., Bayat, A.: Regenerative healing, scar-free healing and scar formation across the species: Current concepts and future perspectives, (2014)

3. Peacock, H.M., Gilbert, E.A.B., Vickaryous, M.K.: Scar-free cutaneous wound healing in the leopard gecko, Eublepharis macularius. J Anat. 227, 596–610 (2015). https://doi.org/10.1111/joa.12368

4. Stoica, A.E., Grumezescu, A.M., Hermenean, A.O., Andronescu, E., Vasile, B.S.: Scar-free healing: Current concepts and future perspectives, (2020)

5. Monavarian, M., Kader, S., Moeinzadeh, S., Jabbari, E.: Regenerative Scar-Free Skin Wound Healing, (2019)

6. Ferguson, M.W.J., O’Kane, S.: Scar-free healing: From embryonic mechanism to adult therapeutic intervention. In: Philosophical Transactions of the Royal Society B: Biological Sciences. pp. 839–850. Royal Society (2004)

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