Nanoengineered self-assembling peptides with increased proteolytic stability promote wound healing

last updated: 2025-02-26
ProjectRePark :: publications list
TitleNanoengineered self-assembling peptides with increased proteolytic stability promote wound healing
Publication TypePapers in Scientific Journals
Year of Publication2025
AuthorsCastro V. I. B., Araújo A. R., Reis R. L., Pashkuleva I., and Pires R. A.
Abstract

The copper complex of the tripeptide glycine–histidine–lysine (GHK) has proven benefits in wound healing and tissue remodeling by promoting blood vessel growth and increasing skin oxygen levels, but its activity is reduced in body fluids due to fast proteolytic cleavage. Herein, we designed several peptides that bear the GHK sequence and can self-assemble into supramolecular nanostructures aiming for enhanced bioactivity. The design involves a phenylalanine (F) backbone known for its ability to form supramolecular assemblies. We tested either coassembly between the structural peptide F4D and the functional sequence GHK or assembly of covalently bound peptides, in which the GHK is bound via the glycine (F4D-GHK) or lysine (F4D-KHG, i.e., inverted GHK sequence). All tested peptides assembled into nanotapes, but their resistance to proteolytic degradation was different: covalently bound peptides generated more stable assemblies. Wound healing assays demonstrated that the supramolecular structures have enhanced bioactivity when compared to GHK alone. Multiplex immunoassay analyses demonstrated the secretion of key regulators of the healing process, such as cytokines, matrix metalloproteinases, and growth factors. Altogether our data show that incorporation of GHK/KHG into supramolecular structures improves its stability, bioactivity, and efficacy in promoting wound healing.

JournalAcs Applied Materials & Interfaces
Volume17
Issue8
Pagination11624 - 11633
Date Published2025-02-12
PublisherAmerican Chemical Society
ISSN1944-8252
DOI10.1021/acsami.4c18221
URLhttps://doi.org/10.1021/acsami.4c18221
Keywordsbioactive peptides, enzymatic degradation, GHK, self-assembly, Wound healing
RightsembargoedAccess (1 Year)
Peer reviewedyes
Statuspublished

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