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Functionalized Peptide Fibrils as a Scaffold for Active Substances in Wound Healing

Abstract

Technological developments in the field of biologically active peptide applications in medicine have increased the need for new methods for peptide delivery. The disadvantage of peptides as drugs is their low biological stability. Recently, great attention has been paid to self-assembling peptides that can form fibrils. Such a formulation makes bioactive peptides more resistant to enzymatic degradation and druggable. Peptide fibrils can be carriers for peptides with interesting biological activities. These features open up prospects for using the peptide fibrils as long-acting drugs and are a valid alternative to conventional peptidic therapies. In our study, we designed new peptide scaffolds that are a hybrid of three interconnected amino acid sequences and are: pro-regenerative, cleavable by neutrophilic elastase, and fibril-forming. We intended to obtain peptides that are stable in the wound environment and that, when applied, would release a biologically active sequence. Our studies showed that the designed hybrid peptides show a high tendency toward regular fibril formation and are able to release the pro-regenerative sequence. Cytotoxicity studies showed that all the designed peptides were safe, did not cause cytotoxic effects and revealed a pro-regenerative potential in human fibroblast and keratinocyte cell lines. In vivo experiments in a dorsal skin injury model in mice indicated that two tested peptides moderately promote tissue repair in their free form. Our research proves that peptide fibrils can be a druggable form and a scaffold for active peptides.

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Category:
Articles
Type:
artykuły w czasopismach
Published in:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES no. 22,
ISSN: 1661-6596
Language:
English
Publication year:
2021
Bibliographic description:
Sawicka J., Iłowska E., Deptuła M., Sosnowski P., Sass P., Czerwiec K., Chmielewska K., Szymańska A., Pietralik-Molińska Z., Kozak M., Sachadyn P., Pikuła M., Rodziewicz-Motowidło S.: Functionalized Peptide Fibrils as a Scaffold for Active Substances in Wound Healing// INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES -Vol. 22,iss. 8 (2021), s.3818-
DOI:
Digital Object Identifier (open in new tab) 10.3390/ijms22083818
Verified by:
Gdańsk University of Technology

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