Topical application of synthetic melanin promotes tissue repair.


Journal

NPJ Regenerative medicine
ISSN: 2057-3995
Titre abrégé: NPJ Regen Med
Pays: United States
ID NLM: 101699846

Informations de publication

Date de publication:
02 Nov 2023
Historique:
received: 12 01 2023
accepted: 22 09 2023
medline: 3 11 2023
pubmed: 3 11 2023
entrez: 3 11 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 37919305
doi: 10.1038/s41536-023-00331-1
pii: 10.1038/s41536-023-00331-1
pmc: PMC10622536
doi:

Types de publication

Journal Article

Langues

eng

Pagination

61

Subventions

Organisme : NIAMS NIH HHS
ID : P30 AR075049
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA060553
Pays : United States
Organisme : NIAMS NIH HHS
ID : U54 AR079795
Pays : United States

Informations de copyright

© 2023. Springer Nature Limited.

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Auteurs

Dauren Biyashev (D)

Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Zofia E Siwicka (ZE)

Department of Chemistry, Northwestern University, Evanston, IL, USA.
International Institute of Nanotechnology, Simpson-Querrey Institute, Chemistry of Life Processes Institute, Lurie Cancer Center. Northwestern University, Evanston, IL, USA.

Ummiye V Onay (UV)

Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Michael Demczuk (M)

Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Dan Xu (D)

Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Madison K Ernst (MK)

Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Spencer T Evans (ST)

Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Cuong V Nguyen (CV)

Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Florencia A Son (FA)

Department of Chemistry, Northwestern University, Evanston, IL, USA.
International Institute of Nanotechnology, Simpson-Querrey Institute, Chemistry of Life Processes Institute, Lurie Cancer Center. Northwestern University, Evanston, IL, USA.

Navjit K Paul (NK)

Department of Chemistry, Northwestern University, Evanston, IL, USA.
International Institute of Nanotechnology, Simpson-Querrey Institute, Chemistry of Life Processes Institute, Lurie Cancer Center. Northwestern University, Evanston, IL, USA.

Naneki C McCallum (NC)

Department of Chemistry, Northwestern University, Evanston, IL, USA.
International Institute of Nanotechnology, Simpson-Querrey Institute, Chemistry of Life Processes Institute, Lurie Cancer Center. Northwestern University, Evanston, IL, USA.

Omar K Farha (OK)

Department of Chemistry, Northwestern University, Evanston, IL, USA.
International Institute of Nanotechnology, Simpson-Querrey Institute, Chemistry of Life Processes Institute, Lurie Cancer Center. Northwestern University, Evanston, IL, USA.
Department of Chemical and Biological Engineering, Northwestern University, Evanston, IL, USA.

Stephen D Miller (SD)

Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

Nathan C Gianneschi (NC)

Department of Chemistry, Northwestern University, Evanston, IL, USA. nathan.gianneschi@northwestern.edu.
International Institute of Nanotechnology, Simpson-Querrey Institute, Chemistry of Life Processes Institute, Lurie Cancer Center. Northwestern University, Evanston, IL, USA. nathan.gianneschi@northwestern.edu.
Department of Materials Science and Engineering, Northwestern University, Evanston, IL, USA. nathan.gianneschi@northwestern.edu.
Department of Biomedical Engineering, Northwestern University, Evanston, IL, USA. nathan.gianneschi@northwestern.edu.
Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. nathan.gianneschi@northwestern.edu.
Department of Chemistry, University of California San Diego, San Diego, Ca, USA. nathan.gianneschi@northwestern.edu.

Kurt Q Lu (KQ)

Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. kurt.lu@northwestern.edu.

Classifications MeSH