Recent advances in the design of artificial corneas

Griffith, May; Harkin, Damien G.

doi:10.1097/icu.0000000000000049

Cited by 33 publications

(19 citation statements)

References 33 publications

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“…The supply of donor corneas for transplantation does not meet the demand in many countries. This prompted researchers to look for alternatives including corneal constructs or equivalents (Griffith and Harkin, 2014). In recent years, there was substantial progress in making corneal stromal constructs based on compressed collagen with or without stromal keratocytes or fibroblasts.…”

Section: Corneal Stromal Wound Healingmentioning

confidence: 99%

“…In recent years, there was substantial progress in making corneal stromal constructs based on compressed collagen with or without stromal keratocytes or fibroblasts. Decellularized corneal stroma has also been used, as well as silk-fibroin or synthetic materials (Griffith and Harkin, 2014). Such constructs can be transplanted into a trephined bed in the stroma to replace damaged tissue, and some have entered clinical trials (Griffith and Harkin, 2014).…”

Section: Corneal Stromal Wound Healingmentioning

confidence: 99%

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Progress in corneal wound healing

Ljubimov

Saghizadeh

2015

Progress in Retinal and Eye Research

637

554

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Corneal wound healing is a complex process involving cell death, migration, proliferation, differentiation, and extracellular matrix remodeling. Many similarities are observed in the healing processes of corneal epithelial, stromal and endothelial cells, as well as cell-specific differences. Corneal epithelial healing largely depends on limbal stem cells and remodeling of the basement membrane. During stromal healing, keratocytes get transformed to motile and contractile myofibroblasts largely due to activation of transforming growth factor-β system. Endothelial cells heal mostly by migration and spreading, with cell proliferation playing a secondary role. In the last decade, many aspects of wound healing process in different parts of the cornea have been elucidated, and some new therapeutic approaches have emerged. The concept of limbal stem cells received rigorous experimental corroboration, with new markers uncovered and new treatment options including gene and microRNA therapy tested in experimental systems. Transplantation of limbal stem cell-enriched cultures for efficient re-epithelialization in stem cell deficiency and corneal injuries has become reality in clinical setting. Mediators and course of events during stromal healing have been detailed, and new treatment regimens including gene (decorin) and stem cell therapy for excessive healing have been designed. This is a very important advance given the popularity of various refractive surgeries entailing stromal wound healing. Successful surgical ways of replacing the diseased endothelium have been clinically tested, and new approaches to accelerate endothelial healing and suppress endothelial-mesenchymal transformation have been proposed including Rho kinase (ROCK) inhibitor eye drops and gene therapy to activate TGF-β inhibitor SMAD7. Promising new technologies with potential for corneal wound healing manipulation including microRNA, induced pluripotent stem cells to generate corneal epithelium, and nanocarriers for corneal drug delivery are discussed. Attention is also paid to problems in wound healing understanding and treatment, such as lack of specific epithelial stem cell markers, reliable identification of stem cells, efficient prevention of haze and stromal scar formation, lack of data on wound regulating microRNAs in keratocytes and endothelial cells, as well as virtual lack of targeted systems for drug and gene delivery to select corneal cells.

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Section: Corneal Stromal Wound Healingmentioning

confidence: 99%

Section: Corneal Stromal Wound Healingmentioning

confidence: 99%

Progress in corneal wound healing

Ljubimov

Saghizadeh

2015

Progress in Retinal and Eye Research

637

554

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“…However, there is a severe worldwide donor shortage, and not all conditions are amenable to donor grafting. 15 Here, hydrogel implants were molded into implants the shape and size of human corneas (500μm thick, 12 mm diam). In compliance with the OECD Principle of Good Laboratory Practice (GLP), ENV/MC/CHEM (98) 17,1997, and with local ethical permission from Stockholms Norra Djurförsöksetiska Nämnd, implants was grafted into the corneas of four Gottingen mini-pigs by anterior lamellar keratoplasty, after excision of the pigs own corneal tissues.…”

Section: Propertiesmentioning

confidence: 99%

Self-assembled collagen-like-peptide implants as alternatives to human donor corneal transplantation

et al. 2016

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Extracellular matrix proteins like collagen promote regeneration as implants in clinical studies. However, collagens are large and unwieldy proteins, making small functional peptide analogs potentially ideal substitutes. Self-assembling collagen-like-peptides conjugated with PEG-maleimide were assembled into hydrogels. When tested pre-clinically as corneal implants in mini-pigs, they promoted cell and nerve regeneration, forming neo-corneas structurally and functionally similar to natural corneas. IntroductionResident stem cells capable of regeneration are present in almost every organ in the body but frequently cannot achieve the repair needed after damage by injury or disease. The limiting factor is often the extracellular matrix (ECM) surrounding the cells. During damage, the ECM is frequently replaced by scar tissue, which does not provide the required structural integrity and inhibits regeneration of functional tissue. 1 The replacement of scar tissue with ECM or biomaterials that mimic its structure and function could therefore promote regeneration. 1,2 Regenerating damaged tissues and organs, including corneas, could potentially mitigate the need for organ transplantation, which currently faces acute worldwide shortage and immune rejection issues. We have previously shown in human corneal transplantation clinical studies that cell-free corneal ECM mimics made from recombinant human collagen (RHC) stimulated regeneration of the human cornea, an organ that normally does not regenerate on its own. 3,4 However, RHC replicates human collagen, which, like many other ECM biopolymers, is comprised of large proteins and is difficult to manipulate. Smaller units of complex proteins, particularly those capable of self-assembly have been examined as controllable ECM mimics, as they can form a wide range of structures including nanofibres. 5 Collagen-like peptides (CLPs), also known as collagen-mimetic peptides (CMPs), have recently been investigated as potential alternatives to collagen, as they can self-assemble and form triple helical nanofibers like collagen. [6][7][8][9][10][11][12][13][14] In order to stabilize the triple helices of CLPs, polymer templates that can link the three peptide chains together with sufficient flexibility to allow for proper packing of the chains with correct amino acid register have been tested. 7 More recent designs have used collagen peptides as the physical crosslinks for the polymer system through triple helix formation. 6,7 CLPs and CLP-polymer systems have now been tested in vitro as engineered 3D scaffolds on their own, 8 conjugated to polyethylene glycol (PEG) backbones, 9-11 and complexed with bioactive factors 12,13 or localization agents such as gold nanoparticles. 14 However, the majority of studies have been confined to in vitro testing with cells.The trend in regenerative medicine is now towards the use of complex, naturally derived ECM macromolecules, as intact decellularised scaffolds or as processed and purified concentrated liquids or finely ground powder that are the...

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“…To date, numerous studies have reported various artificial cornea, including keratoprostheses and tissue-engineered (TE) constructs as alternatives to donor corneas45678. Nevertheless, most of these artificial corneas only partially satisfy the requirements, including biocompatibility, transparency, flexibility, and sufficient suturability strength.…”

mentioning

confidence: 99%

Ultrastructural analysis of the decellularized cornea after interlamellar keratoplasty and microkeratome-assisted anterior lamellar keratoplasty in a rabbit model

Hashimoto

Hattori

Sasaki

et al. 2016

Sci Rep

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The decellularized cornea has received considerable attention for use as an artificial cornea. The decellularized cornea is free from cellular components and other immunogens, but maintains the integrity of the extracellular matrix. However, the ultrastructure of the decellularized cornea has yet to be demonstrated in detail. We investigated the influence of high hydrostatic pressure (HHP) on the decellularization of the corneal ultrastructure and its involvement in transparency, and assessed the in vivo behaviour of the decellularized cornea using two animal transplantation models, in relation to remodelling of collagen fibrils. Decellularized corneas were prepared by the HHP method. The decellularized corneas were executed by haematoxylin and eosin and Masson’s trichrome staining to demonstrate the complete removal of corneal cells. Transmission electron microscopy revealed that the ultrastructure of the decellularized cornea prepared by the HHP method was better maintained than that of the decellularized cornea prepared by the detergent method. The decellularized cornea after interlamellar keratoplasty and microkeratome-assisted anterior lamellar keratoplasty using a rabbit model was stable and remained transparent without ultrastructural alterations. We conclude that the superior properties of the decellularized cornea prepared by the HHP method were attributed to the preservation of the corneal ultrastructure.

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Recent advances in the design of artificial corneas

Cited by 33 publications

References 33 publications

Progress in corneal wound healing

Progress in corneal wound healing

Self-assembled collagen-like-peptide implants as alternatives to human donor corneal transplantation

Ultrastructural analysis of the decellularized cornea after interlamellar keratoplasty and microkeratome-assisted anterior lamellar keratoplasty in a rabbit model

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