In Situ-forming Collagen Hydrogels Crosslinked by Multifunctional Polyethylene Glycol as a Matrix Therapy for Corneal Defects: 2-Month Follow-up in Vivo

Caitlin M. Logan; Gabriella Maria Fernandes-Cunha; Fang Chen; Peter Le; David Mundy; Kyung Sun Na; David Myung

doi:10.1097/ICO.0000000000003104

In Situ-forming Collagen Hydrogels Crosslinked by Multifunctional Polyethylene Glycol as a Matrix Therapy for Corneal Defects: 2-Month Follow-up in Vivo

Caitlin M. Logan, Gabriella Maria Fernandes-Cunha, Fang Chen, Peter Le, David Mundy, Kyung Sun Na, David Myung

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Purpose:We recently showed that in situ-forming collagen gels crosslinked through multifunctional polyethylene glycol (PEG) supported corneal epithelialization 7 days after treatment of lamellar keratectomy wounds. In this study, we aimed to evaluate the longer-term regenerative effects of this gel in animals.Method:Corneal wound healing was assessed 60 days after lamellar keratectomy and gel treatment using slitlamp examination, optical coherence tomography (OCT), pachymetry, corneal topography, an ocular response analyzer, and tonometry. The corneas were evaluated for the presence of beta-tubulin, cytokeratin 3, zonula occludens-1, and alpha smooth muscle actin (SMA) markers. Gene expression of aldehyde dehydrogenase 3A1 (ALDH3A1), cluster of differentiation 31, CD163, alpha-SMA, hepatocyte growth factor, and fibroblast growth factor 2 (FGF-2) and protein expression of CD44 and collagen VI were evaluated.Results:Intraocular pressure, corneal thickness, and hysteresis for the corneas treated with collagen-PEG gels did not significantly change compared with the saline group. However, placido disk topography revealed greater regularity of the central cornea in the gel-treated group compared to the saline group. The gel-treated group exhibited a lower degree of epithelial hyperplasia than the saline group. Immunohistochemical and gene expression analysis showed that the gel-treated corneas exhibited lower alpha-SMA expression compared with the saline group. CD163 and CD44 were found to be elevated in the saline-treated group compared with normal corneas.Conclusions:The in situ-forming collagen-PEG gel promoted epithelialization that improved central corneal topography, epithelial layer morphology, and reduced expression of fibrotic and inflammatory biomarkers after 60 days compared to the saline group.

Original language	English
Pages (from-to)	97-104
Number of pages	8
Journal	Cornea
Volume	42
Issue number	1
DOIs	https://doi.org/10.1097/ICO.0000000000003104
State	Published - 1 Jan 2023

Bibliographical note

Funding Information:
This work was supported by the National Eye Institute, NIH R01 EY033363, K08 EY028176, T32 EY027816, and P30 EY026877), a core grant and Career Development Award from Research to Prevent Blindness (RPB), a grant from the Matilda Ziegler Foundation, the Stanford Spectrum MedTech Pilot Program, the Veterans Affairs Small Projects in Rehabilitation Research (SPiRE) program (I21RX003179), the Harrington Discovery Institute, and the Byers Eye Institute at Stanford. Part of this work was performed at the Stanford Nano Shared Facilities (SNSF), supported by the National Science Foundation under Award ECCS-1542152.

Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.

Keywords

biomaterials
corneal wound healing
epithelial cells
hydrogel
stromal cells

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10.1097/ICO.0000000000003104

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title = "In Situ-forming Collagen Hydrogels Crosslinked by Multifunctional Polyethylene Glycol as a Matrix Therapy for Corneal Defects: 2-Month Follow-up in Vivo",

abstract = "Purpose:We recently showed that in situ-forming collagen gels crosslinked through multifunctional polyethylene glycol (PEG) supported corneal epithelialization 7 days after treatment of lamellar keratectomy wounds. In this study, we aimed to evaluate the longer-term regenerative effects of this gel in animals.Method:Corneal wound healing was assessed 60 days after lamellar keratectomy and gel treatment using slitlamp examination, optical coherence tomography (OCT), pachymetry, corneal topography, an ocular response analyzer, and tonometry. The corneas were evaluated for the presence of beta-tubulin, cytokeratin 3, zonula occludens-1, and alpha smooth muscle actin (SMA) markers. Gene expression of aldehyde dehydrogenase 3A1 (ALDH3A1), cluster of differentiation 31, CD163, alpha-SMA, hepatocyte growth factor, and fibroblast growth factor 2 (FGF-2) and protein expression of CD44 and collagen VI were evaluated.Results:Intraocular pressure, corneal thickness, and hysteresis for the corneas treated with collagen-PEG gels did not significantly change compared with the saline group. However, placido disk topography revealed greater regularity of the central cornea in the gel-treated group compared to the saline group. The gel-treated group exhibited a lower degree of epithelial hyperplasia than the saline group. Immunohistochemical and gene expression analysis showed that the gel-treated corneas exhibited lower alpha-SMA expression compared with the saline group. CD163 and CD44 were found to be elevated in the saline-treated group compared with normal corneas.Conclusions:The in situ-forming collagen-PEG gel promoted epithelialization that improved central corneal topography, epithelial layer morphology, and reduced expression of fibrotic and inflammatory biomarkers after 60 days compared to the saline group.",

keywords = "biomaterials, corneal wound healing, epithelial cells, hydrogel, stromal cells",

author = "Logan, {Caitlin M.} and Fernandes-Cunha, {Gabriella Maria} and Fang Chen and Peter Le and David Mundy and Na, {Kyung Sun} and David Myung",

note = "Funding Information: This work was supported by the National Eye Institute, NIH R01 EY033363, K08 EY028176, T32 EY027816, and P30 EY026877), a core grant and Career Development Award from Research to Prevent Blindness (RPB), a grant from the Matilda Ziegler Foundation, the Stanford Spectrum MedTech Pilot Program, the Veterans Affairs Small Projects in Rehabilitation Research (SPiRE) program (I21RX003179), the Harrington Discovery Institute, and the Byers Eye Institute at Stanford. Part of this work was performed at the Stanford Nano Shared Facilities (SNSF), supported by the National Science Foundation under Award ECCS-1542152. Publisher Copyright: {\textcopyright} 2023 Lippincott Williams and Wilkins. All rights reserved.",

year = "2023",

month = jan,

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doi = "10.1097/ICO.0000000000003104",

language = "English",

volume = "42",

pages = "97--104",

journal = "Cornea",

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T1 - In Situ-forming Collagen Hydrogels Crosslinked by Multifunctional Polyethylene Glycol as a Matrix Therapy for Corneal Defects

T2 - 2-Month Follow-up in Vivo

AU - Logan, Caitlin M.

AU - Fernandes-Cunha, Gabriella Maria

AU - Chen, Fang

AU - Le, Peter

AU - Mundy, David

AU - Na, Kyung Sun

AU - Myung, David

N1 - Funding Information: This work was supported by the National Eye Institute, NIH R01 EY033363, K08 EY028176, T32 EY027816, and P30 EY026877), a core grant and Career Development Award from Research to Prevent Blindness (RPB), a grant from the Matilda Ziegler Foundation, the Stanford Spectrum MedTech Pilot Program, the Veterans Affairs Small Projects in Rehabilitation Research (SPiRE) program (I21RX003179), the Harrington Discovery Institute, and the Byers Eye Institute at Stanford. Part of this work was performed at the Stanford Nano Shared Facilities (SNSF), supported by the National Science Foundation under Award ECCS-1542152. Publisher Copyright: © 2023 Lippincott Williams and Wilkins. All rights reserved.

PY - 2023/1/1

Y1 - 2023/1/1

N2 - Purpose:We recently showed that in situ-forming collagen gels crosslinked through multifunctional polyethylene glycol (PEG) supported corneal epithelialization 7 days after treatment of lamellar keratectomy wounds. In this study, we aimed to evaluate the longer-term regenerative effects of this gel in animals.Method:Corneal wound healing was assessed 60 days after lamellar keratectomy and gel treatment using slitlamp examination, optical coherence tomography (OCT), pachymetry, corneal topography, an ocular response analyzer, and tonometry. The corneas were evaluated for the presence of beta-tubulin, cytokeratin 3, zonula occludens-1, and alpha smooth muscle actin (SMA) markers. Gene expression of aldehyde dehydrogenase 3A1 (ALDH3A1), cluster of differentiation 31, CD163, alpha-SMA, hepatocyte growth factor, and fibroblast growth factor 2 (FGF-2) and protein expression of CD44 and collagen VI were evaluated.Results:Intraocular pressure, corneal thickness, and hysteresis for the corneas treated with collagen-PEG gels did not significantly change compared with the saline group. However, placido disk topography revealed greater regularity of the central cornea in the gel-treated group compared to the saline group. The gel-treated group exhibited a lower degree of epithelial hyperplasia than the saline group. Immunohistochemical and gene expression analysis showed that the gel-treated corneas exhibited lower alpha-SMA expression compared with the saline group. CD163 and CD44 were found to be elevated in the saline-treated group compared with normal corneas.Conclusions:The in situ-forming collagen-PEG gel promoted epithelialization that improved central corneal topography, epithelial layer morphology, and reduced expression of fibrotic and inflammatory biomarkers after 60 days compared to the saline group.

AB - Purpose:We recently showed that in situ-forming collagen gels crosslinked through multifunctional polyethylene glycol (PEG) supported corneal epithelialization 7 days after treatment of lamellar keratectomy wounds. In this study, we aimed to evaluate the longer-term regenerative effects of this gel in animals.Method:Corneal wound healing was assessed 60 days after lamellar keratectomy and gel treatment using slitlamp examination, optical coherence tomography (OCT), pachymetry, corneal topography, an ocular response analyzer, and tonometry. The corneas were evaluated for the presence of beta-tubulin, cytokeratin 3, zonula occludens-1, and alpha smooth muscle actin (SMA) markers. Gene expression of aldehyde dehydrogenase 3A1 (ALDH3A1), cluster of differentiation 31, CD163, alpha-SMA, hepatocyte growth factor, and fibroblast growth factor 2 (FGF-2) and protein expression of CD44 and collagen VI were evaluated.Results:Intraocular pressure, corneal thickness, and hysteresis for the corneas treated with collagen-PEG gels did not significantly change compared with the saline group. However, placido disk topography revealed greater regularity of the central cornea in the gel-treated group compared to the saline group. The gel-treated group exhibited a lower degree of epithelial hyperplasia than the saline group. Immunohistochemical and gene expression analysis showed that the gel-treated corneas exhibited lower alpha-SMA expression compared with the saline group. CD163 and CD44 were found to be elevated in the saline-treated group compared with normal corneas.Conclusions:The in situ-forming collagen-PEG gel promoted epithelialization that improved central corneal topography, epithelial layer morphology, and reduced expression of fibrotic and inflammatory biomarkers after 60 days compared to the saline group.

KW - biomaterials

KW - corneal wound healing

KW - epithelial cells

KW - hydrogel

KW - stromal cells

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DO - 10.1097/ICO.0000000000003104

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AN - SCOPUS:85143379820

SN - 0277-3740

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ER -

In Situ-forming Collagen Hydrogels Crosslinked by Multifunctional Polyethylene Glycol as a Matrix Therapy for Corneal Defects: 2-Month Follow-up in Vivo

Abstract

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Keywords

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