Year: 2023
Type: article
Abstract: In acute skin injury, healing is impaired by the excessive release of reactive oxygen species (ROS). Melanin, an efficient scavenger of radical species in the skin, performs a key role in ROS scavenging in response to UV radiation and is upregulated in response to toxic insult. In a chemical injury model in mice, we demonstrate that the topical application of synthetic melanin particles (SMPs) significantly decreases edema, reduces eschar detachment time, and increases the rate of wound area reduction compared to vehicle controls. Furthermore, these results were replicated in a UV-injury model. Immune array analysis shows downregulated gene expression in apoptotic and inflammatory signaling pathways consistent with histological reduction in apoptosis. Mechanistically, synthetic melanin intervention increases superoxide dismutase (SOD) activity, decreases Mmp9 expression, and suppresses ERK1/2 phosphorylation. Furthermore, we observed that the application of SMPs caused increased populations of anti-inflammatory immune cells to accumulate in the skin, mirroring their decrease from splenic populations. To enhance antioxidant capacity, an engineered biomimetic High Surface Area SMP was deployed, exhibiting increased wound healing efficiency. Finally, in human skin explants, SMP intervention significantly decreased the damage caused by chemical injury. Therefore, SMPs are promising and effective candidates as topical therapies for accelerated wound healing, including via pathways validated in human skin.
Source: npj Regenerative Medicine
Language: English
Topic: Wound Healing and Treatments
Subfield: Rehabilitation
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,790
Funders: National Science Foundation, U.S. Department of Defense, U.S. Department of Health and Human Services, W. M. Keck Foundation, Northwestern University, National Institutes of Health, Defense Threat Reduction Agency, Materials Research Science and Engineering Center, Harvard University, Multidisciplinary University Research Initiative, International Institute for Nanotechnology, Northwestern University, National Cancer Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Division of Materials Research, Division of Electrical, Communications and Cyber Systems, Air Force Office of Scientific Research
Awards: G103610929, G1121383068, G1169090945, G1253704418, G1264094413, G1276186940, G1284175734, NOVEL REACTIVE, POROUS, AND PROCESSABLE POLYMERS FOR CHEM-BIO DEFENSE, G1382277591, TAS::57 3600::TAS '(MURI) UNRAVELING THE BIOLOGY, CHEMISTRY AND NANOSCIENCE OF NATURAL AND SYNTHETIC MELANINS' (TECHNICAL PROPOSAL DATED 15 NOV 2016), G1697802790, G317886719, G322890519, G336680401, G3410623612, G3454132534, G4106000219, G4285583887, G4289625387, G4732266318, MRSEC: Center for Multifunctional Materials, G4912152698, G5218300437, NNCI: Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource, G6544658276, Barrier Damage and The Immune CascadeNorthwestern University CounterACT Center of Excellence (NUCCX), G8073314406, G8230932042, G9000046704, G9000243610, Northwestern University Skin Biology and Diseases Resource-based Center, The Robert H. Lurie Comprehensive Cancer Center
OpenAlex ID: W4388225212