Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels

Sani, Ehsan Shirzaei; Kheirkhah, Ahmad; Rana, Devyesh; Sun, Zhongmou; Foulsham, William; Sheikhi, Amir; Khademhosseini, Ali; Dana, Reza; Annabi, Nasim

doi:10.1126/sciadv.aav1281

Cited by 238 publications

(202 citation statements)

References 47 publications

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“…Alternative treatments for stromal defects are being explored that improve patient outcomes—since there are no technologies specifically approved for the filling and regeneration of stromal defects. Collagen, hyaluronic acid and gelatin based fillers are being investigated as alternatives to the commercially available treatments to provide better biointegration with host tissue 3 , 8 , 26 . These corneal fillers should be degradable and support corneal cell migration and proliferation.…”

Section: Discussionmentioning

confidence: 99%

In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects

Fernandes-Cunha

Chen

et al. 2020

Sci Rep

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Visually significant corneal injuries and subsequent scarring collectively represent a major global human health challenge, affecting millions of people worldwide. Unfortunately, less than 2% of patients who could benefit from a sight-restoring corneal transplant have access to cadaveric donor corneal tissue. Thus, there is a critical need for new ways to repair corneal defects that drive proper epithelialization and stromal remodeling of the wounded area without the need for cadeveric donor corneas. Emerging therapies to replace the need for donor corneas include pre-formed biosynthetic buttons and in situ-forming matrices that strive to achieve the transparency, biocompatibility, patient comfort, and biointegration that is possible with native tissue. Herein, we report on the development of an in situ-forming hydrogel of collagen type I crosslinked via multi-functional polyethylene glycol (PEG)-N-hydroxysuccinimide (NHS) and characterize its biophysical properties and regenerative capacity both in vitro and in vivo. The hydrogels form under ambient conditions within minutes upon mixing without the need for an external catalyst or trigger such as light or heat, and their transparency, degradability, and stiffness are modulated as a function of number of PEG arms and concentration of PEG. In addition, in situ-forming PEG-collagen hydrogels support the migration and proliferation of corneal epithelial and stromal cells on their surface. In vivo studies in which the hydrogels were formed in situ over stromal keratectomy wounds without sutures showed that they supported multi-layered surface epithelialization. Overall, the in situ forming PEG-collagen hydrogels exhibited physical and biological properties desirable for a corneal stromal defect wound repair matrix that could be applied without the need for sutures or an external trigger such as a catalyst or light energy.

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Section: Discussionmentioning

confidence: 99%

In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects

Fernandes-Cunha

Chen

et al. 2020

Sci Rep

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“…Unlike most chemical crosslinking processes that are cytotoxic, the main advantage of using GelMA is that the cells can be mixed into the material prior to crosslinking. GelMA has been used to engineer stromal scaffolds,157 endothelial sheets,162 and as a corneal bioadhesive 169. Gelatin has also been combined with other materials to improve its mechanical properties, cell response and degradation rate including collagen, chitosan, chondroitin sulfate, and hyaluronic acid 145–147,155b,156…”

Section: Materials Selectionmentioning

confidence: 99%

Designing Scaffolds for Corneal Regeneration

Ahearne

Fernández‐Pérez

Masterton

et al. 2020

Adv Funct Materials

112

109

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Corneal blindness is one of the most common causes of vision loss worldwide, affecting millions of people. To treat these patients, researchers have been examining different approaches to engineer corneal scaffolds suitable for transplantation. Scaffolds have been developed to replace part or all of the cornea depending on the patient requirements. Both acellular and cell-seeded scaffolds have been tested in animal models. Materials that have been under investigation for manufacturing scaffolds include collagen, silk fibroin, amniotic membrane, decellularized cornea, fibrin, chitosan, gelatin, agarose, alginate, and hyaluronic acid in addition to several synthetic polymers. Different combinations of materials, fiber crosslinking techniques, and incorporation of bioactive molecules have also been examined. Factors such as the physical properties, cytocompatibility, degradation behavior, and optical characteristics have to be considered when selecting a suitable scaffold material. Recent advancements in materials fabrication techniques such as bioprinting, electrospinning, and different collagen alignment techniques, allow scaffolds to be generated that more accurately mimic the structure of the corneal stroma. A number of scaffolds have commenced clinical trials to determine their suitability for corneal regeneration.

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“…This technology, called GelCORE (gel for corneal regeneration) has been developed as an adhesive biomaterial to treat corneal stromal loss. 61 The biomaterial is natural and acellular in that it is derived from porcine gelatin that is stabilized by addition of methacrylic anhydride. 62 The result is a tough but elastic and transparent biomaterial that can be photopolymerized using visible blue light, thereby avoiding exposure of eye structures to the potentially damaging UV light normally used to photocure polymers.…”

Section: Tissue Adhesive Gelmentioning

confidence: 99%

Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential

Lagali

2019

Current Eye Research

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The corneal stroma comprises 90% of the corneal thickness and is critical for the cornea's transparency and refractive function necessary for vision. When the corneal stroma is altered by disease, injury, or scarring, however, an irreversible loss of transparency can occur. Corneal stromal pathology is the cause of millions of cases of blindness globally, and although corneal transplantation is the standard therapy, a severe global deficit of donor corneal tissue and eye banking infrastructure exists, and is unable to meet the overwhelming need. An alternative approach is to harness the endogenous regenerative ability of the corneal stroma, which exhibits self-renewal of the collagenous extracellular matrix under appropriate conditions. To mimic endogenous stromal regeneration, however, is a challenge. Unlike the corneal epithelium and endothelium, the corneal stroma is an exquisitely organized extracellular matrix containing stromal cells, proteoglycans and corneal nerves that is difficult to recapitulate in vitro. Nevertheless, much progress has recently been made in developing stromal equivalents, and in this review the most recent approaches to stromal regeneration therapy are described and discussed. Novel approaches for stromal regeneration include human or animal corneal and/or non-corneal tissue that is acellular or is decellularized and/or recellularized, acellular bioengineered stromal scaffolds, tissue adhesives, 3D bioprinting and stromal stem cell therapy. This review highlights the techniques and advances that have achieved first clinical use or are close to translation for eventual therapeutic application in repairing and regenerating the corneal stroma, while the potential of these novel therapies for achieving effective stromal regeneration is discussed. ARTICLE HISTORY

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Sutureless repair of corneal injuries using naturally derived bioadhesive hydrogels

Cited by 238 publications

References 47 publications

In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects

In situ-forming collagen hydrogel crosslinked via multi-functional PEG as a matrix therapy for corneal defects

Designing Scaffolds for Corneal Regeneration

Corneal Stromal Regeneration: Current Status and Future Therapeutic Potential

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