Therapeutic efficacy of BSA formulated hydrogels in corneal wound healing and epithelial cell regeneration: an ex vivo study

Abstract Corneal injury requires both epithelial regeneration and stromal repair, and formulated biomaterials established to repair damaged corneas can be used in regenerative medicine. The challenge is to ensure that biomaterials can be incorporated into the host tissue and delivered intracellularl...

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Main Authors: Ramachandran Samivel, Mana A. Alanazi, Adnan A. Khan, Ali M. Masmali, Saud A. Alanazi, Turki Almubrad, Saeed Akhtar
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-04408-3
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author Ramachandran Samivel
Mana A. Alanazi
Adnan A. Khan
Ali M. Masmali
Saud A. Alanazi
Turki Almubrad
Saeed Akhtar
author_facet Ramachandran Samivel
Mana A. Alanazi
Adnan A. Khan
Ali M. Masmali
Saud A. Alanazi
Turki Almubrad
Saeed Akhtar
author_sort Ramachandran Samivel
collection DOAJ
description Abstract Corneal injury requires both epithelial regeneration and stromal repair, and formulated biomaterials established to repair damaged corneas can be used in regenerative medicine. The challenge is to ensure that biomaterials can be incorporated into the host tissue and delivered intracellularly without causing rapid material deprivation, thus maintaining corneal transparency. Bovine serum albumin-formulated hydrogels (BHG) were prepared by dissolving with riboflavin, retinoic acid, and 2.5% glutaraldehyde solutions. Periphery-centered wounds from camel corneas (8mm diameter and 250 µm depth) were mounted on a dome-shaped agarose gel in six-well plates containing BHG-supplemented serum-free Medium 199. The plates were then incubated at 37 °C for 24, 48, and 72 h. A complete set of corneoscleral rings was procured and processed for histopathological, electron microscopy, and immunohistochemistry assays. Histological and electron microscopy results showed that all epithelial layers and anterior stroma developed faster in the BHG-treated wounds than in the untreated wounded corneas. Compared to untreated wounded corneas, BHG-treated corneas accumulated higher levels of fibronectin and ki-67 and lower levels of alpha-smooth muscle actin inductions. BHG-treated corneal wounds healed faster than untreated wounded corneas. Overall, BHG enhances epithelial regeneration and strengthens the stromal architecture by upregulating ECM and growth factors. Hence, BHG is a promising therapeutic hydrogel for wounded corneas, and further studies on corneal stromal wound healing and epithelial cell reimbursement in an in vivo model are required.
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spelling doaj-art-6b4e23bb14e54138819209d08a91fd142025-08-20T02:30:46ZengNature PortfolioScientific Reports2045-23222025-06-0115111710.1038/s41598-025-04408-3Therapeutic efficacy of BSA formulated hydrogels in corneal wound healing and epithelial cell regeneration: an ex vivo studyRamachandran Samivel0Mana A. Alanazi1Adnan A. Khan2Ali M. Masmali3Saud A. Alanazi4Turki Almubrad5Saeed Akhtar6Cornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud UniversityCornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud UniversityCornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud UniversityCornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud UniversityCornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud UniversityCornea Research Chair, Department of Optometry, College of Applied Medical Sciences, King Saud UniversityCollege of Applied Medical Sciences, Inaya Medical SciencesAbstract Corneal injury requires both epithelial regeneration and stromal repair, and formulated biomaterials established to repair damaged corneas can be used in regenerative medicine. The challenge is to ensure that biomaterials can be incorporated into the host tissue and delivered intracellularly without causing rapid material deprivation, thus maintaining corneal transparency. Bovine serum albumin-formulated hydrogels (BHG) were prepared by dissolving with riboflavin, retinoic acid, and 2.5% glutaraldehyde solutions. Periphery-centered wounds from camel corneas (8mm diameter and 250 µm depth) were mounted on a dome-shaped agarose gel in six-well plates containing BHG-supplemented serum-free Medium 199. The plates were then incubated at 37 °C for 24, 48, and 72 h. A complete set of corneoscleral rings was procured and processed for histopathological, electron microscopy, and immunohistochemistry assays. Histological and electron microscopy results showed that all epithelial layers and anterior stroma developed faster in the BHG-treated wounds than in the untreated wounded corneas. Compared to untreated wounded corneas, BHG-treated corneas accumulated higher levels of fibronectin and ki-67 and lower levels of alpha-smooth muscle actin inductions. BHG-treated corneal wounds healed faster than untreated wounded corneas. Overall, BHG enhances epithelial regeneration and strengthens the stromal architecture by upregulating ECM and growth factors. Hence, BHG is a promising therapeutic hydrogel for wounded corneas, and further studies on corneal stromal wound healing and epithelial cell reimbursement in an in vivo model are required.https://doi.org/10.1038/s41598-025-04408-3HydrogelRetinoic acidRiboflavinBovine serum albuminCorneal-scleraOrgan culture
spellingShingle Ramachandran Samivel
Mana A. Alanazi
Adnan A. Khan
Ali M. Masmali
Saud A. Alanazi
Turki Almubrad
Saeed Akhtar
Therapeutic efficacy of BSA formulated hydrogels in corneal wound healing and epithelial cell regeneration: an ex vivo study
Scientific Reports
Hydrogel
Retinoic acid
Riboflavin
Bovine serum albumin
Corneal-sclera
Organ culture
title Therapeutic efficacy of BSA formulated hydrogels in corneal wound healing and epithelial cell regeneration: an ex vivo study
title_full Therapeutic efficacy of BSA formulated hydrogels in corneal wound healing and epithelial cell regeneration: an ex vivo study
title_fullStr Therapeutic efficacy of BSA formulated hydrogels in corneal wound healing and epithelial cell regeneration: an ex vivo study
title_full_unstemmed Therapeutic efficacy of BSA formulated hydrogels in corneal wound healing and epithelial cell regeneration: an ex vivo study
title_short Therapeutic efficacy of BSA formulated hydrogels in corneal wound healing and epithelial cell regeneration: an ex vivo study
title_sort therapeutic efficacy of bsa formulated hydrogels in corneal wound healing and epithelial cell regeneration an ex vivo study
topic Hydrogel
Retinoic acid
Riboflavin
Bovine serum albumin
Corneal-sclera
Organ culture
url https://doi.org/10.1038/s41598-025-04408-3
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