Abstract

Given the incidence of corneal dysfunctions and diseases worldwide and the limited availability of healthy, human donors, investigators are working to generate engineered cellular and acellular therapeutic approaches as alternatives to corneal transplants from human cadavers. These engineered strategies aim to address existing complications with human corneal transplants, including graft rejection, infection, and complications resulting from surgical methodologies. The main goals of these research endeavors are to (1) determine ideal mechanical properties, (2) devise methodologies to improve the efficacy of engineered corneal grafts and cell-based therapies, and (3) optimize transplantation of engineered tissue structures in the eye. Thus, recent innovations have sought to address these challenges through both in vitro and in vivo studies. This review covers recent work aimed at evaluating engineered materials, potential therapeutic cells, and the resulting cell-material interactions that lead to optimal corneal graft properties. Furthermore, we discuss promising strategies in corneal tissue engineering techniques and in vivo studies in animal models.

Highlights

  • Films prepared from AA had a 1.5 higher fold change in the elastic modulus compared to Bombyx mori and Philosamia ricini (PR) silk films, while maintaining similar level of transparency

  • Many cell types have been investigated for use in corneal tissue engineering, including corneal endothelial cells (CEnCs), corneal epithelial cells (CEpCs), corneal epithelial stem cells (CEpSCs), keratocytes (CKs), mesenchymal stem cells (MSCs), adipose-tissue derived stem cells (ASCs), and embryonic-derived stem cells [132,133,134]

  • 14, there were no changes in the expression of paxillin and integrin β-1. They hypothesize that actin re-organization continues to mediate downstream signaling over time, while the expression of integrin β-1 may be decreased after initial cell attachment

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Summary

Cornea Structure and Clinical Motivations for Engineered Therapies

Corneal injuries and defects resulting in vision loss affect over 1 million new patients worldwide each year [1]. While recent replacements [5,21,22], the scope of this review covers the use of natural biopolymers in work aimed at understanding mechanical properties of natural engineered materials, cellthe generation of transplantable tissues or in vitro cornea mimics. While advancements exist the of materials for corneal replacements [5,21,22], of this review covers thesynthetic use of natural biopolymers in the generation of recent transplantable tissues or ininvitro cornea mimics. We emphasize recent advancements exist in the usethe ofscope synthetic materials foruse corneal replacements [5,21,22], the generation of transplantable tissues orproperties in vitro cornea mimics.

Engineering a Cornea Mimetic
Natural Biopolymer-Based Hydrogels as Cornea Mimics
Silk Fibroin Hydrogels
Collagen-Based Hydrogels
Gelatin and GelMA Based Hydrogels
Films and Non-Hydrogel-Based Scaffolds as Cornea Mimics
Silk Fibroin Films
Collagen Films and Electrospun Mats
Decellularized Corneal Tissues
Cells for Corneal Epithelium
Cells for Corneal Stroma
Cells for Corneal Endothelium
Combining Cell Types for Partial and Full Thickness Mimics
Investigations of Natural Biopolymer-Based Engineered Corneas in
Silk Fibroin and Its Use in Pre-Clinical Models
Collagen-Based Materials in Pre-Clinical Models
Gelatin and GelMA Materials in Pre-Clinical Investigations
Decellularized Corneas
Findings
Outlook
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