Bio-orthogonal crosslinking and hyaluronan facilitate transparent healing after treatment of deep corneal injuries with in situ-forming hydrogels

Abstract Corneal transplantation is the primary treatment for corneal blindness, affecting millions globally. However, challenges like donor scarcity and surgical complications remain. Recently, in situ-forming corneal stroma substitutes have emerged, offering potential solutions to these limitation...

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Main Authors: Fang Chen, Uiyoung Han, Thitima Wungcharoen, Youngyoon Amy Seo, Peter Le, Li Jiang, Nae-Won Kang, Euisun Song, Kyeongwoo Jang, David Mundy, Gabriella Maria Fernandes-Cunha, Sarah Heilshorn, David Myung
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:npj Regenerative Medicine
Online Access:https://doi.org/10.1038/s41536-024-00385-9
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author Fang Chen
Uiyoung Han
Thitima Wungcharoen
Youngyoon Amy Seo
Peter Le
Li Jiang
Nae-Won Kang
Euisun Song
Kyeongwoo Jang
David Mundy
Gabriella Maria Fernandes-Cunha
Sarah Heilshorn
David Myung
author_facet Fang Chen
Uiyoung Han
Thitima Wungcharoen
Youngyoon Amy Seo
Peter Le
Li Jiang
Nae-Won Kang
Euisun Song
Kyeongwoo Jang
David Mundy
Gabriella Maria Fernandes-Cunha
Sarah Heilshorn
David Myung
author_sort Fang Chen
collection DOAJ
description Abstract Corneal transplantation is the primary treatment for corneal blindness, affecting millions globally. However, challenges like donor scarcity and surgical complications remain. Recently, in situ-forming corneal stroma substitutes have emerged, offering potential solutions to these limitations. These substitutes enable liquid-to-hydrogel formation in situ, eliminating sutures and reducing complications. Here we performed a direct, side-by-side comparison of a composite hyaluronan-collagen (HA-Col) hydrogel crosslinked by either photochemistry or bio-orthogonal chemistry to ascertain the impact of reaction specificity on corneal wound healing. Testing in rodent and rabbit models suggests that composite HA-Col gels crosslinked by bio-orthogonal chemistry results in more rapid and optically favorable wound healing compared to the same composition crosslinked by photochemistry as well as bio-orthogonally crosslinked collagen alone. These findings underscore biochemical parameters that may be important to the success of crosslinked, in situ-forming hydrogels as an alternative to corneal transplantation, with the potential for expanded access to treatment and improved outcomes.
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publishDate 2025-02-01
publisher Nature Portfolio
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series npj Regenerative Medicine
spelling doaj-art-2b9b64cc2bbb4aa7a9252158d0b05b3f2025-02-09T12:16:21ZengNature Portfolionpj Regenerative Medicine2057-39952025-02-0110111110.1038/s41536-024-00385-9Bio-orthogonal crosslinking and hyaluronan facilitate transparent healing after treatment of deep corneal injuries with in situ-forming hydrogelsFang Chen0Uiyoung Han1Thitima Wungcharoen2Youngyoon Amy Seo3Peter Le4Li Jiang5Nae-Won Kang6Euisun Song7Kyeongwoo Jang8David Mundy9Gabriella Maria Fernandes-Cunha10Sarah Heilshorn11David Myung12Spencer Center for Vision Research, Byers Eye Institute, Stanford University School of MedicineSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of MedicineSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of MedicineSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of MedicineSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of MedicineSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of MedicineSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of MedicineSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of MedicineSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of MedicineSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of MedicineSpencer Center for Vision Research, Byers Eye Institute, Stanford University School of MedicineMaterials Science and Engineering, Stanford UniversitySpencer Center for Vision Research, Byers Eye Institute, Stanford University School of MedicineAbstract Corneal transplantation is the primary treatment for corneal blindness, affecting millions globally. However, challenges like donor scarcity and surgical complications remain. Recently, in situ-forming corneal stroma substitutes have emerged, offering potential solutions to these limitations. These substitutes enable liquid-to-hydrogel formation in situ, eliminating sutures and reducing complications. Here we performed a direct, side-by-side comparison of a composite hyaluronan-collagen (HA-Col) hydrogel crosslinked by either photochemistry or bio-orthogonal chemistry to ascertain the impact of reaction specificity on corneal wound healing. Testing in rodent and rabbit models suggests that composite HA-Col gels crosslinked by bio-orthogonal chemistry results in more rapid and optically favorable wound healing compared to the same composition crosslinked by photochemistry as well as bio-orthogonally crosslinked collagen alone. These findings underscore biochemical parameters that may be important to the success of crosslinked, in situ-forming hydrogels as an alternative to corneal transplantation, with the potential for expanded access to treatment and improved outcomes.https://doi.org/10.1038/s41536-024-00385-9
spellingShingle Fang Chen
Uiyoung Han
Thitima Wungcharoen
Youngyoon Amy Seo
Peter Le
Li Jiang
Nae-Won Kang
Euisun Song
Kyeongwoo Jang
David Mundy
Gabriella Maria Fernandes-Cunha
Sarah Heilshorn
David Myung
Bio-orthogonal crosslinking and hyaluronan facilitate transparent healing after treatment of deep corneal injuries with in situ-forming hydrogels
npj Regenerative Medicine
title Bio-orthogonal crosslinking and hyaluronan facilitate transparent healing after treatment of deep corneal injuries with in situ-forming hydrogels
title_full Bio-orthogonal crosslinking and hyaluronan facilitate transparent healing after treatment of deep corneal injuries with in situ-forming hydrogels
title_fullStr Bio-orthogonal crosslinking and hyaluronan facilitate transparent healing after treatment of deep corneal injuries with in situ-forming hydrogels
title_full_unstemmed Bio-orthogonal crosslinking and hyaluronan facilitate transparent healing after treatment of deep corneal injuries with in situ-forming hydrogels
title_short Bio-orthogonal crosslinking and hyaluronan facilitate transparent healing after treatment of deep corneal injuries with in situ-forming hydrogels
title_sort bio orthogonal crosslinking and hyaluronan facilitate transparent healing after treatment of deep corneal injuries with in situ forming hydrogels
url https://doi.org/10.1038/s41536-024-00385-9
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