In Situ-Forming Collagen-Hyaluronate Semi-Interpenetrating Network Hydrogel Enhances Corneal Defect Repair

Chen, Fang; Mundy, David; Le, Peter; Seo, Youngyoon Amy; Logan, Caitlin; Fernandes-Cunha, Gabriella; Basco, Chris A; Myung, David

doi:10.1167/tvst.11.10.22

Cited by 5 publications

(4 citation statements)

References 86 publications

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“…Because of the prominent involvement of the immunological component, it is also possible that the remaining scarred tissue is not repairable by the qCSKs. The second strategy, hence, involves the removal of scar tissue, which will then be replaced by a biomaterial, such as collagen or hyaluronic acid 42 , 43 , encapsulated with qCSKs. The biomaterial would act as a temporary scaffold, permitting time for the qCSKs to secrete the ECM proper and organize the collagen fibers.…”

Section: Discussionmentioning

confidence: 99%

Impact of keratocyte differentiation on corneal opacity resolution and visual function recovery in male rats

Riau,

Look,

Yam

et al. 2024

Nat Commun

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Intrastromal cell therapy utilizing quiescent corneal stromal keratocytes (qCSKs) from human donor corneas emerges as a promising treatment for corneal opacities, aiming to overcome limitations of traditional surgeries by reducing procedural complexity and donor dependency. This investigation demonstrates the therapeutic efficacy of qCSKs in a male rat model of corneal stromal opacity, underscoring the significance of cell-delivery quality and keratocyte differentiation in mediating corneal opacity resolution and visual function recovery. Quiescent CSKs-treated rats display improvements in escape latency and efficiency compared to wounded, non-treated rats in a Morris water maze, demonstrating improved visual acuity, while stromal fibroblasts-treated rats do not. Advanced imaging, including multiphoton microscopy, small-angle X-ray scattering, and transmission electron microscopy, revealed that qCSK therapy replicates the native cornea’s collagen fibril morphometry, matrix order, and ultrastructural architecture. These findings, supported by the expression of keratan sulfate proteoglycans, validate qCSKs as a potential therapeutic solution for corneal opacities.

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Section: Discussionmentioning

confidence: 99%

Impact of keratocyte differentiation on corneal opacity resolution and visual function recovery in male rats

Riau,

Look,

Yam

et al. 2024

Nat Commun

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“…The results obtained were promising: The hydrogel, which is made of 97% water and is highly transparent, demonstrated excellent cytocompatibility and the ability to support epithelialization both in vitro and in vivo. More recently, an in situ-forming semi-interpenetrating polymer network (SIPN) hydrogel was investigated by the same group of authors in the same animal model [60]: The hydrogel demonstrated mechanical and optical properties similar to those of the native cornea, reducing stromal defect size compared with controls, and promoting multilayered epithelization.…”

Section: Biomaterials For Cornea Replacement and Restorationmentioning

confidence: 99%

Replace or Regenerate? Diverse Approaches to Biomaterials for Treating Corneal Lesions

Bonato,

Bagno

2024

Biomimetics

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The inner structures of the eye are protected by the cornea, which is a transparent membrane exposed to the external environment and subjected to the risk of lesions and diseases, sometimes resulting in impaired vision and blindness. Several eye pathologies can be treated with a keratoplasty, a surgical procedure aimed at replacing the cornea with tissues from human donors. Even though the success rate is high (up to 90% for the first graft in low-risk patients at 5-year follow-up), this approach is limited by the insufficient number of donors and several clinically relevant drawbacks. Alternatively, keratoprosthesis can be applied in an attempt to restore minimal functions of the cornea: For this reason, it is used only for high-risk patients. Recently, many biomaterials of both natural and synthetic origin have been developed as corneal substitutes to restore and replace diseased or injured corneas in low-risk patients. After illustrating the traditional clinical approaches, the present paper aims to review the most innovative solutions that have been recently proposed to regenerate the cornea, avoiding the use of donor tissues. Finally, innovative approaches to biological tissue 3D printing and xenotransplantation will be mentioned.

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“…Hydrogels alone or together with cells as "repair patch" filling in corneal defects can be categorized into 2 classes: synthetic and naturally derived hydrogels. To name a few, cyanoacrylates, 24 polyethylene glycol, 25 collagen, 26,27 fibrin, 28 alginate, 29 chitosan, 16 gelatin, 30 and decellularized extracellular matrix (ECM) 31 have been studied for corneal repair. Synthetic hydrogels are easy to customize and preferable in meeting certain desired properties, but they may not promote tissue regeneration.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal Stem Cell–Laden In Situ–Forming Hydrogel for Preventing Corneal Stromal Opacity

Liu,

Hong

2024

Cornea

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Purpose: The aims of this study were to construct a mesenchymal stem cell (MSC)-laden in situ–forming hydrogel and study its effects on preventing corneal stromal opacity. Methods: The native gellan gum was modified by high temperature and pressure, and the rabbit bone marrow MSCs were encapsulated before adding Ca2+ to initiate cross-linking. The effects of the hydrogel on 3D culture and gene expression of the rabbit bone marrow MSCs were observed in vitro. Then, the MSC–hydrogel was used to repair corneal stromal injury in New Zealand white rabbits within 28 days postoperation. Results: The short-chain gellan gum solution has a very low viscosity (<0.1 Pa·s) that is ideal for encapsulating cells. Moreover, mRNA expressions of 3D-cultured MSCs coding for corneal stromal components (decorin, lumican, and keratocan) were upregulated (by 127.8, 165.5, and 25.4 times, respectively) (P < 0.05) on day 21 in vitro and were verified by Western blotting results. For the in vivo study, the corneal densitometry of the experimental group was (20.73 ± 1.85) grayscale units which was lower than the other groups (P < 0.05). The MSC–hydrogel downregulated mRNA expression coding for fibrosis markers (α-smooth muscle actin, vimentin, collagen type 5-α1, and collagen type 1-α1) in the rabbit corneal stroma. Furthermore, some of the 5-ethynyl-2’-deoxyuridine (EdU)-labeled MSCs integrated into the upper corneal stroma and expressed keratocyte-specific antigens on day 28 postoperation. Conclusions: The short-chain gellan gum allows MSCs to slowly release to the corneal stromal defect and prevent corneal stromal opacity. Some of the implanted MSCs can integrate into the corneal stroma and differentiate into keratocytes.

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In Situ-Forming Collagen-Hyaluronate Semi-Interpenetrating Network Hydrogel Enhances Corneal Defect Repair

Cited by 5 publications

References 86 publications

Impact of keratocyte differentiation on corneal opacity resolution and visual function recovery in male rats

Impact of keratocyte differentiation on corneal opacity resolution and visual function recovery in male rats

Replace or Regenerate? Diverse Approaches to Biomaterials for Treating Corneal Lesions

Mesenchymal Stem Cell–Laden In Situ–Forming Hydrogel for Preventing Corneal Stromal Opacity

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