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

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 t...

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Autores principales: Sawicka, Justyna, Iłowska, Emilia, Deptuła, Milena, Sosnowski, Paweł, Sass, Piotr, Czerwiec, Katarzyna, Chmielewska, Klaudia, Szymańska, Aneta, Pietralik-Molińska, Zuzanna, Kozak, Maciej, Sachadyn, Paweł, Pikuła, Michał, Rodziewicz-Motowidło, Sylwia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067766/
https://www.ncbi.nlm.nih.gov/pubmed/33917000
http://dx.doi.org/10.3390/ijms22083818
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author Sawicka, Justyna
Iłowska, Emilia
Deptuła, Milena
Sosnowski, Paweł
Sass, Piotr
Czerwiec, Katarzyna
Chmielewska, Klaudia
Szymańska, Aneta
Pietralik-Molińska, Zuzanna
Kozak, Maciej
Sachadyn, Paweł
Pikuła, Michał
Rodziewicz-Motowidło, Sylwia
author_facet Sawicka, Justyna
Iłowska, Emilia
Deptuła, Milena
Sosnowski, Paweł
Sass, Piotr
Czerwiec, Katarzyna
Chmielewska, Klaudia
Szymańska, Aneta
Pietralik-Molińska, Zuzanna
Kozak, Maciej
Sachadyn, Paweł
Pikuła, Michał
Rodziewicz-Motowidło, Sylwia
author_sort Sawicka, Justyna
collection PubMed
description 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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spelling pubmed-80677662021-04-25 Functionalized Peptide Fibrils as a Scaffold for Active Substances in Wound Healing Sawicka, Justyna Iłowska, Emilia Deptuła, Milena Sosnowski, Paweł Sass, Piotr Czerwiec, Katarzyna Chmielewska, Klaudia Szymańska, Aneta Pietralik-Molińska, Zuzanna Kozak, Maciej Sachadyn, Paweł Pikuła, Michał Rodziewicz-Motowidło, Sylwia Int J Mol Sci Article 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. MDPI 2021-04-07 /pmc/articles/PMC8067766/ /pubmed/33917000 http://dx.doi.org/10.3390/ijms22083818 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sawicka, Justyna
Iłowska, Emilia
Deptuła, Milena
Sosnowski, Paweł
Sass, Piotr
Czerwiec, Katarzyna
Chmielewska, Klaudia
Szymańska, Aneta
Pietralik-Molińska, Zuzanna
Kozak, Maciej
Sachadyn, Paweł
Pikuła, Michał
Rodziewicz-Motowidło, Sylwia
Functionalized Peptide Fibrils as a Scaffold for Active Substances in Wound Healing
title Functionalized Peptide Fibrils as a Scaffold for Active Substances in Wound Healing
title_full Functionalized Peptide Fibrils as a Scaffold for Active Substances in Wound Healing
title_fullStr Functionalized Peptide Fibrils as a Scaffold for Active Substances in Wound Healing
title_full_unstemmed Functionalized Peptide Fibrils as a Scaffold for Active Substances in Wound Healing
title_short Functionalized Peptide Fibrils as a Scaffold for Active Substances in Wound Healing
title_sort functionalized peptide fibrils as a scaffold for active substances in wound healing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067766/
https://www.ncbi.nlm.nih.gov/pubmed/33917000
http://dx.doi.org/10.3390/ijms22083818
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