Corneal Cell Matrix‐Conditioned Amniotic Membrane with Improved Biochemical Properties and Corneal Wound Healing Potential: An In Vitro and In Vivo Study

Abstract Several attempts have been made to engineer the amniotic membrane (AM) to improve its biomechanical and biological characteristics close to corneal tissue for corneal wound dressing applications. In this study, a decellularized AM (dAM) is conditioned with limbal epithelial stem cells (LESC...

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Main Authors: Zeinab Nokhbedehghan, Zahra Esmaeili, Seyed‐Hashem Daryabari, Hossein Aghamollaei, Sara Simorgh, Jila Majidi, Sanaz Alizadeh, Sadjad Khosravimelal, Narendra Pal Singh Chauhan, Hajar Nasiri, Mazaher Gholipourmalekabadi
Format: Article
Language:English
Published: Wiley-VCH 2025-06-01
Series:Macromolecular Materials and Engineering
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Online Access:https://doi.org/10.1002/mame.202400390
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author Zeinab Nokhbedehghan
Zahra Esmaeili
Seyed‐Hashem Daryabari
Hossein Aghamollaei
Sara Simorgh
Jila Majidi
Sanaz Alizadeh
Sadjad Khosravimelal
Narendra Pal Singh Chauhan
Hajar Nasiri
Mazaher Gholipourmalekabadi
author_facet Zeinab Nokhbedehghan
Zahra Esmaeili
Seyed‐Hashem Daryabari
Hossein Aghamollaei
Sara Simorgh
Jila Majidi
Sanaz Alizadeh
Sadjad Khosravimelal
Narendra Pal Singh Chauhan
Hajar Nasiri
Mazaher Gholipourmalekabadi
author_sort Zeinab Nokhbedehghan
collection DOAJ
description Abstract Several attempts have been made to engineer the amniotic membrane (AM) to improve its biomechanical and biological characteristics close to corneal tissue for corneal wound dressing applications. In this study, a decellularized AM (dAM) is conditioned with limbal epithelial stem cells (LESCs) by freeze‐thawing (cAM), and fully characterized in vitro for mechanical behaviors, degradation, and cytobiocompatibility, and in vivo implantation in comparison with dAM. The LESCs‐conditioning improved the LESCs adhesion property of cAM compared with dAM with no cytotoxicity against LESCs in both dAM and cAM. Complete epithelial coverage with improved corneal wound healing and collagen synthesis, and also no scarring is observed in the wounds treated with dAM and cAM. Notably, in the cAM group, epithelial layers are well delaminated and collagen fibers are arranged in a basket weave pattern. A significant up‐regulation in limbal/epithelial genes (ABCG2 and Ck3) expression is observed in the wounds treated with cAM, compared with other groups. Both dAM and cAM significantly down‐regulated the pro‐inflammatory genes (IL6 and TNFα), compared with the control wound. In conclusion, this study reveals that LESCs‐conditioning is a viable strategy for the development of corneal wound dressing and now promises to proceed with clinical investigations.
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publishDate 2025-06-01
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series Macromolecular Materials and Engineering
spelling doaj-art-6cced3f9cd3d410fb07c8847fcf5a0642025-08-20T03:45:23ZengWiley-VCHMacromolecular Materials and Engineering1438-74921439-20542025-06-013106n/an/a10.1002/mame.202400390Corneal Cell Matrix‐Conditioned Amniotic Membrane with Improved Biochemical Properties and Corneal Wound Healing Potential: An In Vitro and In Vivo StudyZeinab Nokhbedehghan0Zahra Esmaeili1Seyed‐Hashem Daryabari2Hossein Aghamollaei3Sara Simorgh4Jila Majidi5Sanaz Alizadeh6Sadjad Khosravimelal7Narendra Pal Singh Chauhan8Hajar Nasiri9Mazaher Gholipourmalekabadi10Cellular and Molecular Research Center Iran University of Medical Sciences Tehran 1416634793 IranCellular and Molecular Research Center Iran University of Medical Sciences Tehran 1416634793 IranVision Health Research Center Semnan University of Medical Sciences Semnan 3513119111 IranVision Health Research Center Semnan University of Medical Sciences Semnan 3513119111 IranCellular and Molecular Research Center Iran University of Medical Sciences Tehran 1416634793 IranCellular and Molecular Research Center Iran University of Medical Sciences Tehran 1416634793 IranR & D Department Royan Stem Cell Technology Co Tehran 1665666311 IranDepartment of Materials Science and Engineering Faculty of Engineering Monash University Clayton Victoria 3800 AustraliaDepartment of Chemistry Faculty of Science Bhupal Nobles’ University Udaipur Rajasthan 313002 IndiaCellular and Molecular Research Center Iran University of Medical Sciences Tehran 1416634793 IranCellular and Molecular Research Center Iran University of Medical Sciences Tehran 1416634793 IranAbstract Several attempts have been made to engineer the amniotic membrane (AM) to improve its biomechanical and biological characteristics close to corneal tissue for corneal wound dressing applications. In this study, a decellularized AM (dAM) is conditioned with limbal epithelial stem cells (LESCs) by freeze‐thawing (cAM), and fully characterized in vitro for mechanical behaviors, degradation, and cytobiocompatibility, and in vivo implantation in comparison with dAM. The LESCs‐conditioning improved the LESCs adhesion property of cAM compared with dAM with no cytotoxicity against LESCs in both dAM and cAM. Complete epithelial coverage with improved corneal wound healing and collagen synthesis, and also no scarring is observed in the wounds treated with dAM and cAM. Notably, in the cAM group, epithelial layers are well delaminated and collagen fibers are arranged in a basket weave pattern. A significant up‐regulation in limbal/epithelial genes (ABCG2 and Ck3) expression is observed in the wounds treated with cAM, compared with other groups. Both dAM and cAM significantly down‐regulated the pro‐inflammatory genes (IL6 and TNFα), compared with the control wound. In conclusion, this study reveals that LESCs‐conditioning is a viable strategy for the development of corneal wound dressing and now promises to proceed with clinical investigations.https://doi.org/10.1002/mame.202400390amniotic membranecorneal tissue engineeringcorneal wound dressingextracellular matrixstem cells conditioning
spellingShingle Zeinab Nokhbedehghan
Zahra Esmaeili
Seyed‐Hashem Daryabari
Hossein Aghamollaei
Sara Simorgh
Jila Majidi
Sanaz Alizadeh
Sadjad Khosravimelal
Narendra Pal Singh Chauhan
Hajar Nasiri
Mazaher Gholipourmalekabadi
Corneal Cell Matrix‐Conditioned Amniotic Membrane with Improved Biochemical Properties and Corneal Wound Healing Potential: An In Vitro and In Vivo Study
Macromolecular Materials and Engineering
amniotic membrane
corneal tissue engineering
corneal wound dressing
extracellular matrix
stem cells conditioning
title Corneal Cell Matrix‐Conditioned Amniotic Membrane with Improved Biochemical Properties and Corneal Wound Healing Potential: An In Vitro and In Vivo Study
title_full Corneal Cell Matrix‐Conditioned Amniotic Membrane with Improved Biochemical Properties and Corneal Wound Healing Potential: An In Vitro and In Vivo Study
title_fullStr Corneal Cell Matrix‐Conditioned Amniotic Membrane with Improved Biochemical Properties and Corneal Wound Healing Potential: An In Vitro and In Vivo Study
title_full_unstemmed Corneal Cell Matrix‐Conditioned Amniotic Membrane with Improved Biochemical Properties and Corneal Wound Healing Potential: An In Vitro and In Vivo Study
title_short Corneal Cell Matrix‐Conditioned Amniotic Membrane with Improved Biochemical Properties and Corneal Wound Healing Potential: An In Vitro and In Vivo Study
title_sort corneal cell matrix conditioned amniotic membrane with improved biochemical properties and corneal wound healing potential an in vitro and in vivo study
topic amniotic membrane
corneal tissue engineering
corneal wound dressing
extracellular matrix
stem cells conditioning
url https://doi.org/10.1002/mame.202400390
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