Progress in the development of a corneal replacement: keratoprostheses and tissue-engineered corneas

Abstract

Rapid progress has been made in the past 5 years in the development of corneal replacements. Traditionally they are divided into two categories, keratoprostheses and tissue-engineered corneal equivalents, as replacement tissues are increasingly in demand worldwide. There are currently several different keratoprosthesis models in clinical use around the world. The most popular and most widely publicized is the AlphaCor model, which has enjoyed significant clinical success. However, improvements remain to be made, and the aim of most of the current research is to better understand the interactions between a synthetic material and the surrounding biology on a more fundamental level. This improved understanding will no doubt lead to improvements in current models and to the development of new models in the near future. While tissue-engineered corneal equivalents have been under investigation for considerably less time, there is growing evidence to suggest that a tissue-engineered corneal equivalent comprised of primarily natural materials will exist in the not too distant future. Research groups have reported strong in vitro and in vivo results. The strength of the collagen matrix and its ability to support cell infiltration have been the primary avenues of research. Various collagen crosslinking techniques have been used. Infiltration of three major cells of the cornea has been observed. Most importantly, the ability of these materials to support nerve ingrowth has been demonstrated. While challenges remain with both types of corneal replacements, the considerable progress in the recent past suggests that reliable implants for the treatment of a variety of corneal diseases will be available. This review will provide an overview of recent results, and will provide insight into the future of research on corneal replacements.

Corneal endothelium: developmental strategies for regeneration

“…67 However, clinically available procedures with artificial corneas have limitations such as inflammation of the retroprosthetic membrane and development of glaucoma, and are reserved for high-risk patients. 68,69 The limited availability of donor corneas and the current issues in surgical procedures require the development of new methods in the field of tissue engineering in order to improve corneal endothelial cell survival and increase corneal endothelial cell density. The emergent strategies in the field of cell biology and tissue cultivation of corneal endothelial cells aim at the production of transplantable endothelial cell sheets.…”

Processing Porcine Cornea for Biomedical Applications

“…However, the shortage of donor tissue is a significant and growing problem; in North America, waiting lists exceeding 2 years are now common. 2,3 The cornea donor pool is expected to shrink as the population ages; not only are older patients less-appropriate donors, but also they are more likely to require transplants. Moreover, the shortage is expected to be compounded by the increasing incidence of transmissible diseases such as HIV, hepatitis, and Creutzfeldt-Jakob disease, and the growing popularity of refractive surgery because these surgically treated corneas are unacceptable as donor tissue.…”

“…However, at present, there are no clinically usable substitutes because of problems related to biocompatibility and mechanical or optical properties. 2,3 Consequently, xenogeneic corneas are worthy of investigation as a human replacement. Xenografts are more readily available and are convenient for clinical application, except with regard to their xenoimmunogenicity.…”

Regeneration of Corneal Cells and Nerves in an Implanted Collagen Corneal Substitute

“…During wound healing, ECM macromolecules help provide cues for repair and regeneration, serving as ''regeneration templates.'' 1 The human cornea is the optically clear, tough covering in front of the eye that is responsible for most light transmission and refraction to the retina for vision. It is avascular and has 3 main cellular layers.…”