Skin wound (modified from Dermatology Center of Indiana, https://dermindy.com/skin-injury-how-do-wounds-heal/)
Skin injury remains a major health concern that needs attention. In the United States alone, Medicare costs for wound treatments were estimated to range from $28.1 billion to $96.8 billion annually. A recent study has determined that the prevalence of long-term or chronic wounds in adults is 1.67 per 1000 persons. The staggering high costs associated with and the prevalence of skin injuries among the population have a huge impact on the economy and the well-being of the people. Thus, there is a need for the development of more effective and efficient therapies for skin wounds.
Skin wounds and oxidative stress
When you injure your skin, your skin tissue initiates and undergoes repair. This physiological process is a complex one that is orchestrated and mediated by a number of cell types within the skin tissue and a host of biological molecules. The wound healing process can be a relatively short one (2-4 weeks) or it can be longer (more than 4 weeks). Skin wounds with a short healing time can be considered acute wounds whereas skin wounds that take a much longer time to heal (more than 4 weeks) are chronic wounds.
Numerous factors including age, sex, chronic diseases, and immunosuppression affect skin tissue repair. One of the major mechanisms underlying impaired wound healing and chronic wounds is oxidative stress. Our cells generate a class of biochemicals known as reactive oxygen species in response to tissue injury. External stimuli to the skin such as exposure to ultraviolet light will also result in an elevation of reactive oxygen species levels. This increase in the levels of reactive oxygen species can trigger oxidative stress.
What are reactive oxygen species?
Reactive oxygen species are molecules containing oxygen with added electrons, a subatomic particle that carries a negative charge. Examples of reactive oxygen species include hydroxyl radicals, hydrogen peroxide, and peroxide. Chemical reactions that lead to the formation of reactive oxygen species are referred to as oxidation reactions. Although low levels of reactive oxygen species are beneficial to wound healing, high levels of these biochemicals can be harmful, leading to oxidative stress. At high levels, reactive oxygen species can react with other biomolecules in the cell such as DNA, lipid, and protein, and damage these molecules.
Our cells do have molecules that mitigate the effects of reactive oxygen species. Enzymes such as superoxide dismutase and antioxidant molecules such as vitamin C and vitamin E serve as electron donors and reactive oxygen species scavengers respectively. Nevertheless, an excessive surge in the levels of reactive oxygen species within cells may throw off the balance between the levels of reactive oxygen species and antioxidants causing oxidative stress.
Melanin promotes wound healing
Recently, scientists from Northwestern University and the University of California at San Diego reported that the application of synthetic melanin on skin wounds accelerated the wound healing process. Melanin is a polymer formed from the amino acid tyrosine. It is responsible for the pigmentation of our skin, eyes, and hair. Within skin tissue, melanin is produced by a class of cells known as melanocytes. This biomolecule has been shown to be an antioxidant and scavenger of reactive oxygen species.
The scientists examined the effects of synthetic melanin on two mouse models of skin wounds. One model involved treating mice skin with nitrogen-mustard, a chemical that induces skin injury and the other model involved exposing mice to ultraviolet light. In both models, synthetic melanin reduced tissue swelling and decreased the time for dead tissue to shed off from skin when compared to control experiments. Synthetic melanin also increased the rate of wound area reduction. There was a reduction in cells undergoing programmed cell death in the skin wounds of mice treated with synthetic melanin. In line with this, the scientists observed a suppression in the levels of molecules involved in the chemical pathway mediating the programmed cell death process. Synthetic melanin also promoted blood vessel formation in the wounds of mice. In addition, the activity of superoxide dismutase, an enzyme that catalyzes the reaction that degrades reactive oxygen species, was elevated in mouse skin tissue subjected to nitrogen-mustard exposure to induce wounding and treated with synthetic melanin.
The scientists also generated synthetic melanin molecules with high surface area and tested these molecules on skin wounds of mice induced by nitrogen-mustard. They found that application of synthetic melanin with a high surface area to skin wounds accelerated skin tissue repair compared to mice exposed to synthetic melanin with a low surface area and to mice with skin wounds treated with deionized water (as control).
Examination of mouse models was complemented with studies using human skin explants, human skin tissues grown in nutrient medium. Nitrogen-mustard was applied to these skin explants to induce wounding. Tissue repair was then assessed following exposure to synthetic melanin. Histological analysis revealed that synthetic melanin treatment minimized tissue damage when compared to control skin explants that were injured but not treated with melanin. Melanin-treated skin explants displayed a reduction in cells undergoing programmed cell death. Separation between the outermost layer of skin known as epidermis and the layer below, the dermis, was decreased in injured skin explant tissues exposed to synthetic melanin when compared to injured tissues not treated with synthetic melanin.
This investigation reveals synthetic melanin as a potential candidate for treating skin wounds. Further therapeutic development and clinical testing will be required before synthetic melanin can be used in the clinic.
References
https://my.clevelandclinic.org/health/body/22615-melanin#:~:text=What%20is%20melanin%3F,eye%2C%20hair%20and%20skin%20color.
Biyashev D, Siwicka ZE, Onay UV, Demczuk M, Xu D, Ernst MK, Evans ST, Nguyen CV, Son FA, Paul NK, McCallum NC, Farha OK, Miller SD, Gianneschi NC, Lu KQ. Topical application of synthetic melanin promotes tissue repair. NPJ Regen Med. 2023 Nov 2;8(1):61. doi: 10.1038/s41536-023-00331-1.
Dunnill C, Patton T, Brennan J, Barrett J, Dryden M, Cooke J, Leaper D, Georgopoulos NT. Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process. Int Wound J. 2017 Feb;14(1):89-96. doi: 10.1111/iwj.12557.
Martinengo L, Olsson M, Bajpai R, Soljak M, Upton Z, Schmidtchen A, Car J, Järbrink K. Prevalence of chronic wounds in the general population: systematic review and meta-analysis of observational studies. Ann Epidemiol. 2019 Jan;29:8-15. doi: 10.1016/j.annepidem.2018.10.005.
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Thomas Hess, Cathy BSN, RN, CWOCN. Checklist for Factors Affecting Wound Healing. Advances in Skin & Wound Care 24(4):p 192, April 2011. | DOI: 10.1097/01.ASW.0000396300.04173.ec
Xu, H., Zheng, Y.-W., Liu, Q., Liu, L.-P., Luo, F.-L., Zhou, H.-C., … Li, Y.-M. (2018). Reactive Oxygen Species in Skin Repair, Regeneration, Aging, and Inflammation. InTech. doi: 10.5772/intechopen.72747
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