Cargando…

Growth Factor Binding Peptides in Poly (Ethylene Glycol) Diacrylate (PEGDA)-Based Hydrogels for an Improved Healing Response of Human Dermal Fibroblasts

Growth factors (GF) are critical cytokines in wound healing. However, the direct delivery of these biochemical cues into a wound site significantly increases the cost of wound dressings and can lead to a strong immunological response due to the introduction of a foreign source of GFs. To overcome th...

Descripción completa

Detalles Bibliográficos
Autores principales: Clevenger, Abigail J., Jimenez-Vergara, Andrea C., Tsai, Erin H., de Barros Righes, Gabriel, Díaz-Lasprilla, Ana M., Ramírez-Caballero, Gustavo E., Munoz-Pinto, Dany J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857753/
https://www.ncbi.nlm.nih.gov/pubmed/36661794
http://dx.doi.org/10.3390/gels9010028
_version_ 1784873935409512448
author Clevenger, Abigail J.
Jimenez-Vergara, Andrea C.
Tsai, Erin H.
de Barros Righes, Gabriel
Díaz-Lasprilla, Ana M.
Ramírez-Caballero, Gustavo E.
Munoz-Pinto, Dany J.
author_facet Clevenger, Abigail J.
Jimenez-Vergara, Andrea C.
Tsai, Erin H.
de Barros Righes, Gabriel
Díaz-Lasprilla, Ana M.
Ramírez-Caballero, Gustavo E.
Munoz-Pinto, Dany J.
author_sort Clevenger, Abigail J.
collection PubMed
description Growth factors (GF) are critical cytokines in wound healing. However, the direct delivery of these biochemical cues into a wound site significantly increases the cost of wound dressings and can lead to a strong immunological response due to the introduction of a foreign source of GFs. To overcome this challenge, we designed a poly(ethylene glycol) diacrylate (PEGDA) hydrogel with the potential capacity to sequester autologous GFs directly from the wound site. We demonstrated that synthetic peptide sequences covalently tethered to PEGDA hydrogels physically retained human transforming growth factor beta 1 (hTGFβ1) and human vascular endothelial growth factor (hVEGF) at 3.2 and 0.6 ng/mm(2), respectively. In addition, we demonstrated that retained hTGFβ1 and hVEGF enhanced human dermal fibroblasts (HDFa) average cell surface area and proliferation, respectively, and that exposure to both GFs resulted in up to 1.9-fold higher fraction of area covered relative to the control. After five days in culture, relative to the control surface, non-covalently bound hTGFβ1 significantly increased the expression of collagen type I and hTGFβ1 and downregulated vimentin and matrix metalloproteinase 1 expression. Cumulatively, the response of HDFa to hTGFβ1 aligns well with the expected response of fibroblasts during the early stages of wound healing.
format Online
Article
Text
id pubmed-9857753
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-98577532023-01-21 Growth Factor Binding Peptides in Poly (Ethylene Glycol) Diacrylate (PEGDA)-Based Hydrogels for an Improved Healing Response of Human Dermal Fibroblasts Clevenger, Abigail J. Jimenez-Vergara, Andrea C. Tsai, Erin H. de Barros Righes, Gabriel Díaz-Lasprilla, Ana M. Ramírez-Caballero, Gustavo E. Munoz-Pinto, Dany J. Gels Article Growth factors (GF) are critical cytokines in wound healing. However, the direct delivery of these biochemical cues into a wound site significantly increases the cost of wound dressings and can lead to a strong immunological response due to the introduction of a foreign source of GFs. To overcome this challenge, we designed a poly(ethylene glycol) diacrylate (PEGDA) hydrogel with the potential capacity to sequester autologous GFs directly from the wound site. We demonstrated that synthetic peptide sequences covalently tethered to PEGDA hydrogels physically retained human transforming growth factor beta 1 (hTGFβ1) and human vascular endothelial growth factor (hVEGF) at 3.2 and 0.6 ng/mm(2), respectively. In addition, we demonstrated that retained hTGFβ1 and hVEGF enhanced human dermal fibroblasts (HDFa) average cell surface area and proliferation, respectively, and that exposure to both GFs resulted in up to 1.9-fold higher fraction of area covered relative to the control. After five days in culture, relative to the control surface, non-covalently bound hTGFβ1 significantly increased the expression of collagen type I and hTGFβ1 and downregulated vimentin and matrix metalloproteinase 1 expression. Cumulatively, the response of HDFa to hTGFβ1 aligns well with the expected response of fibroblasts during the early stages of wound healing. MDPI 2022-12-29 /pmc/articles/PMC9857753/ /pubmed/36661794 http://dx.doi.org/10.3390/gels9010028 Text en © 2022 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
Clevenger, Abigail J.
Jimenez-Vergara, Andrea C.
Tsai, Erin H.
de Barros Righes, Gabriel
Díaz-Lasprilla, Ana M.
Ramírez-Caballero, Gustavo E.
Munoz-Pinto, Dany J.
Growth Factor Binding Peptides in Poly (Ethylene Glycol) Diacrylate (PEGDA)-Based Hydrogels for an Improved Healing Response of Human Dermal Fibroblasts
title Growth Factor Binding Peptides in Poly (Ethylene Glycol) Diacrylate (PEGDA)-Based Hydrogels for an Improved Healing Response of Human Dermal Fibroblasts
title_full Growth Factor Binding Peptides in Poly (Ethylene Glycol) Diacrylate (PEGDA)-Based Hydrogels for an Improved Healing Response of Human Dermal Fibroblasts
title_fullStr Growth Factor Binding Peptides in Poly (Ethylene Glycol) Diacrylate (PEGDA)-Based Hydrogels for an Improved Healing Response of Human Dermal Fibroblasts
title_full_unstemmed Growth Factor Binding Peptides in Poly (Ethylene Glycol) Diacrylate (PEGDA)-Based Hydrogels for an Improved Healing Response of Human Dermal Fibroblasts
title_short Growth Factor Binding Peptides in Poly (Ethylene Glycol) Diacrylate (PEGDA)-Based Hydrogels for an Improved Healing Response of Human Dermal Fibroblasts
title_sort growth factor binding peptides in poly (ethylene glycol) diacrylate (pegda)-based hydrogels for an improved healing response of human dermal fibroblasts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9857753/
https://www.ncbi.nlm.nih.gov/pubmed/36661794
http://dx.doi.org/10.3390/gels9010028
work_keys_str_mv AT clevengerabigailj growthfactorbindingpeptidesinpolyethyleneglycoldiacrylatepegdabasedhydrogelsforanimprovedhealingresponseofhumandermalfibroblasts
AT jimenezvergaraandreac growthfactorbindingpeptidesinpolyethyleneglycoldiacrylatepegdabasedhydrogelsforanimprovedhealingresponseofhumandermalfibroblasts
AT tsaierinh growthfactorbindingpeptidesinpolyethyleneglycoldiacrylatepegdabasedhydrogelsforanimprovedhealingresponseofhumandermalfibroblasts
AT debarrosrighesgabriel growthfactorbindingpeptidesinpolyethyleneglycoldiacrylatepegdabasedhydrogelsforanimprovedhealingresponseofhumandermalfibroblasts
AT diazlasprillaanam growthfactorbindingpeptidesinpolyethyleneglycoldiacrylatepegdabasedhydrogelsforanimprovedhealingresponseofhumandermalfibroblasts
AT ramirezcaballerogustavoe growthfactorbindingpeptidesinpolyethyleneglycoldiacrylatepegdabasedhydrogelsforanimprovedhealingresponseofhumandermalfibroblasts
AT munozpintodanyj growthfactorbindingpeptidesinpolyethyleneglycoldiacrylatepegdabasedhydrogelsforanimprovedhealingresponseofhumandermalfibroblasts