Synthetic melanin speeds healing of skin wounds by scavenging harmful reactive oxygen molecules and reducing inflammation
by Science Writer Kim Woolcock
In severe skin injuries, healing can be slowed by overproduction of reactive oxygen species (ROS), highly reactive molecules that damage tissue, leading to inflammation. Although artificial antioxidant wound-healing compounds have been tested, biocompatibility and delivery pose issues. Now, researchers are testing the power of synthetic melanin to heal skin injuries. Melanin is commonly known as the pigment found in hair, skin, and eyes, but it is also a potent antioxidant and free radical scavenger, providing natural defense in the skin. Researchers hypothesized that synthetic melanin might offer an excellent natural option to promote wound healing. In an open-access paper published November 2, 2023 in npj Regenerative Medicine, Biyashev et al. report that skin injuries heal significantly more quickly if treated with synthetic melanin. The paper is titled “Topical Application of Synthetic Melanin Promotes Tissue Repair Melanocytes.”
Melanin is produced by melanocytes and comes in many different forms. In the skin, melanin provides protection against UV radiation. It is also a potent scavenger of free radicals. ROS contain one or more unpaired electrons, making them highly reactive. They are a natural product of metabolism, but in excess they damage cells and tissues. Melanin contains electron-rich functional groups that allow it to disarm ROS, protecting tissues against their harmful effects.
The researchers hypothesized that applying a synthetic version of the skin’s own repair compound could boost wound healing. To create synthetic melanin particles (SMPs), the scientists polymerized dopamine (Editor’s note: In the body, dopamine spontaneously forms a melanin through a process called melanogenesis.) They created two forms of synthetic melanin: one similar to natural melanin (non-porous, low surface area) and a porous version with greater surface area. The more porous version was expected to have greater effect. Neither SMP was absorbed when applied to skin; both remained on the skin surface. The porous version had slightly higher antioxidant capacity (90%) than the non-porousversion(80%), but both were similar to other antioxidants, such as eugenol or ascorbic acid.
To test the wound-healing capacity of the SMPs, the researchers used a mouse model with skin injury induced by UV light or nitrogen mustard, a blistering agent that damages DNA and kills cells; it is used in chemotherapy and is chemically similar to sulfur mustard, otherwise known as mustard gas.
Both SMPs significantly improved wound healing, reducing inflammation and swelling, and shrinking wound area and depth more quickly than without treatment; as predicted, the porous SMP had a stronger effect than the non-porous SMP. After 14 days, wounds of mice treated with either SMPwere just a few millimeters in diameter, whereas those of untreated mice were still ~50% of their diameter on Day 1 (12 mm).
Investigating how synthetic melanin application improved wound healing revealed two main mechanisms. First, SMP application boosted levels of immune cells at the wound site. SMP-treated mice had increased populations of several important types of immune cells (CD206hi inflammatory monocytes, non-inflammatory monocytes, and macrophages). The spleen, a reservoir of immune cells, was depleted in these same populations of immune cells, indicating that SMP application had enhanced chemoattraction of immune cells to the wound site.
Second, in addition to its own antioxidant activity, SMP boosted levels of antioxidant enzymes such as superoxide dismutase (SOD), which converts damaging ROS into oxygen and hydrogen peroxide. Treatment with synthetic melanin boosted levels of SOD at the wound site. The researchers confirmed the effect by using a SOD inhibitor; applying both SMP and a SOD inhibitor mostly erased the effect of the SMP. The researchers note that the two effects are likely complementary; the hydrogen peroxide produced as SOD disarms ROS is a powerful second messenger that attracts immune cells to wound sites.
Final testing on human skin, using samples donated after surgery, showed that, just as in mice, SMP application dramatically improved wound healing. This test was limited by the fact that it was performed ex vivo, so the skin was not supplied with circulation or a reservoir of immune cells to recruit from. However, it does indicate the potential of the treatment.
Overall, synthetic melanin improves recovery from skin injury by acting as a natural antioxidant, boosting activity of antioxidant enzymes, and increasing populations of immune cells, reducing inflammation and speeding healing. This biomimetic wound-healing therapy essentially turns up the volume on the body’s own response to damage, promoting tissue repair after chemical or UV-induced injury. Synthetic melanin shows potential for future therapeutic development.