Bioartificial human corneas generated by tissue engineering. A historical and technical review.

Area of Science:

• Ophthalmology
• Regenerative Medicine
• Biomaterials Science

Background:

• Bioartificial corneas are engineered using cells, biomaterials, and bioactive molecules for corneal tissue engineering.
• Corneal cells can be orthotypical (epithelial, stromal, endothelial) or heterotypical (e.g., mesenchymal stem cells).
• Biomaterials include decellularized natural tissues or de novo synthetic/natural materials like collagen, fibrin, and agarose.

Purpose of the Study:

• To review the development of bioartificial corneas and assess their suitability for clinical translation.
• To identify challenges and bottlenecks in the progression of bioartificial cornea research from basic science to clinical application.
• To highlight the need for improved preclinical characterization and novel clinical studies for advanced corneal therapies.

Main Methods:

• Literature review of studies on bioartificial cornea generation and clinical translation.
• Analysis of requirements for advanced therapy medicinal products and regulatory authorization.
• Evaluation of existing authorized corneal substitutes and clinical trial data.

Main Results:

• Most bioartificial corneas do not meet the stringent requirements for clinical translation and regulatory approval.
• Partial corneal substitutes, often single-cell types with scaffolds, are more common than fully engineered corneas.
• Only one advanced therapy medicinal product, NANOULCOR, a human bioartificial cornea, has been evaluated in patients.

Conclusions:

• A significant gap exists between basic research and clinical application for bioartificial corneas.
• Current bioartificial cornea technologies face hurdles in preclinical characterization and regulatory pathways.
• Novel clinical studies are essential to advance corneal tissue engineering and improve outcomes beyond existing therapies.