Regenerative Approaches as Alternatives to Donor Allografting for Restoration of Corneal Function

Abstract

A range of alternatives to human donor tissue for corneal transplantation are being developed to address the shortfall of good quality tissues as well as the clinical conditions for which allografting is contraindicated. Classical keratoprostheses, commonly referred to as artificial corneas, are being used clinically to replace minimal corneal function. However, they are used only as last resorts, as they are associated with significant complications, such as extrusion/rejection, glaucoma, and retinal detachment. The past few years have seen significant developments in technologies designed to replace part or the full thickness of damaged or diseased corneas with materials that encourage regeneration to different extents. This review describes selected examples of these corneal substitutes, which range from cell-based regenerative strategies to keratoprostheses with regenerative capabilities via tissue-engineered scaffolds pre-seeded with stem cells. It is unlikely that one corneal substitute will be best for all indications, but taken together, the various approaches may soon be able to supplement the supply of human donor corneas for transplantation or allow restoration of diseased or damaged corneas that cannot be treated by currently available techniques.<p>Funding Agencies|Swedish Research Council, County Council of Ostergotland, Sweden||Canadian Stem Cell Network||NSERC Canada|SAF2011-22500|Spanish Ministerio de Economia y Competitividad||</p

Composite core-and-skirt collagen hydrogels with differential degradation for corneal therapeutic applications

“…Natural collagen-derived corneal scaffolds are the most mature of these [13][14][15][16][17][18][19], and we recently reported results from collagen-based scaffolds four years after implantation into diseased human corneas [13]. These cell-free scaffolds replaced the extracellular matrix, allowing host cells and nerves to eventually grow over and around the scaffold [13].…”

Nano-Engineered Biomaterials for Tissue Regeneration: What Has Been Achieved So Far?

“…Currently, refractive eye surgeries and synthetic corneal replacements (keratoprostheses) are applied to combat this issue but are limited in several ways. Primarily, post-operative complications, such as infection, are rampant for many patients (Griffith et al, 2012). Furthermore, synthetics are incompatible at times depending on the individual and are at risk of biological rejection and induction of further ocular problems (Griffith et al, 2012).…”

“…Primarily, post-operative complications, such as infection, are rampant for many patients (Griffith et al, 2012). Furthermore, synthetics are incompatible at times depending on the individual and are at risk of biological rejection and induction of further ocular problems (Griffith et al, 2012). Biocompatible and bioactive nanomaterials can possibly minimize complications associated with corneal regeneration.…”

Thermo-responsive cell culture carriers based on poly(vinyl methyl ether)—the effect of biomolecular ligands to balance cell adhesion and stimulated detachment

“…The lack of adequate corneal donor tissue with a sufficient endothelial cell density and quality prompted to the establishment of novel therapeutic approaches and techniques. Various tissue engineering strategies were developed during the last decades [20], including the generation of corneal endothelial cell sheets that were directly transplanted onto de-endothelialized corneas [21]. So far, these approaches were only experimental and did not reach clinical application in humans [22].…”