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In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects

Visually significant corneal injuries and subsequent scarring collectively represent a major global human health challenge, affecting millions of people worldwide. Unfortunately, less than 2% of patients who could benefit from a sight-restoring corneal transplant have access to cadaveric donor corne...

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Autores principales: Fernandes-Cunha, Gabriella Maria, Chen, Karen Mei, Chen, Fang, Le, Peter, Han, Ju Hee, Mahajan, Leela Ann, Lee, Hyun Jong, Na, Kyung Sun, Myung, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542443/
https://www.ncbi.nlm.nih.gov/pubmed/33028837
http://dx.doi.org/10.1038/s41598-020-72978-5
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author Fernandes-Cunha, Gabriella Maria
Chen, Karen Mei
Chen, Fang
Le, Peter
Han, Ju Hee
Mahajan, Leela Ann
Lee, Hyun Jong
Na, Kyung Sun
Myung, David
author_facet Fernandes-Cunha, Gabriella Maria
Chen, Karen Mei
Chen, Fang
Le, Peter
Han, Ju Hee
Mahajan, Leela Ann
Lee, Hyun Jong
Na, Kyung Sun
Myung, David
author_sort Fernandes-Cunha, Gabriella Maria
collection PubMed
description Visually significant corneal injuries and subsequent scarring collectively represent a major global human health challenge, affecting millions of people worldwide. Unfortunately, less than 2% of patients who could benefit from a sight-restoring corneal transplant have access to cadaveric donor corneal tissue. Thus, there is a critical need for new ways to repair corneal defects that drive proper epithelialization and stromal remodeling of the wounded area without the need for cadeveric donor corneas. Emerging therapies to replace the need for donor corneas include pre-formed biosynthetic buttons and in situ-forming matrices that strive to achieve the transparency, biocompatibility, patient comfort, and biointegration that is possible with native tissue. Herein, we report on the development of an in situ-forming hydrogel of collagen type I crosslinked via multi-functional polyethylene glycol (PEG)-N-hydroxysuccinimide (NHS) and characterize its biophysical properties and regenerative capacity both in vitro and in vivo. The hydrogels form under ambient conditions within minutes upon mixing without the need for an external catalyst or trigger such as light or heat, and their transparency, degradability, and stiffness are modulated as a function of number of PEG arms and concentration of PEG. In addition, in situ-forming PEG-collagen hydrogels support the migration and proliferation of corneal epithelial and stromal cells on their surface. In vivo studies in which the hydrogels were formed in situ over stromal keratectomy wounds without sutures showed that they supported multi-layered surface epithelialization. Overall, the in situ forming PEG-collagen hydrogels exhibited physical and biological properties desirable for a corneal stromal defect wound repair matrix that could be applied without the need for sutures or an external trigger such as a catalyst or light energy.
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spelling pubmed-75424432020-10-14 In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects Fernandes-Cunha, Gabriella Maria Chen, Karen Mei Chen, Fang Le, Peter Han, Ju Hee Mahajan, Leela Ann Lee, Hyun Jong Na, Kyung Sun Myung, David Sci Rep Article Visually significant corneal injuries and subsequent scarring collectively represent a major global human health challenge, affecting millions of people worldwide. Unfortunately, less than 2% of patients who could benefit from a sight-restoring corneal transplant have access to cadaveric donor corneal tissue. Thus, there is a critical need for new ways to repair corneal defects that drive proper epithelialization and stromal remodeling of the wounded area without the need for cadeveric donor corneas. Emerging therapies to replace the need for donor corneas include pre-formed biosynthetic buttons and in situ-forming matrices that strive to achieve the transparency, biocompatibility, patient comfort, and biointegration that is possible with native tissue. Herein, we report on the development of an in situ-forming hydrogel of collagen type I crosslinked via multi-functional polyethylene glycol (PEG)-N-hydroxysuccinimide (NHS) and characterize its biophysical properties and regenerative capacity both in vitro and in vivo. The hydrogels form under ambient conditions within minutes upon mixing without the need for an external catalyst or trigger such as light or heat, and their transparency, degradability, and stiffness are modulated as a function of number of PEG arms and concentration of PEG. In addition, in situ-forming PEG-collagen hydrogels support the migration and proliferation of corneal epithelial and stromal cells on their surface. In vivo studies in which the hydrogels were formed in situ over stromal keratectomy wounds without sutures showed that they supported multi-layered surface epithelialization. Overall, the in situ forming PEG-collagen hydrogels exhibited physical and biological properties desirable for a corneal stromal defect wound repair matrix that could be applied without the need for sutures or an external trigger such as a catalyst or light energy. Nature Publishing Group UK 2020-10-07 /pmc/articles/PMC7542443/ /pubmed/33028837 http://dx.doi.org/10.1038/s41598-020-72978-5 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Fernandes-Cunha, Gabriella Maria
Chen, Karen Mei
Chen, Fang
Le, Peter
Han, Ju Hee
Mahajan, Leela Ann
Lee, Hyun Jong
Na, Kyung Sun
Myung, David
In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects
title In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects
title_full In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects
title_fullStr In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects
title_full_unstemmed In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects
title_short In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects
title_sort in situ-forming collagen hydrogel crosslinked via multi-functional peg as a matrix therapy for corneal defects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542443/
https://www.ncbi.nlm.nih.gov/pubmed/33028837
http://dx.doi.org/10.1038/s41598-020-72978-5
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