State-of-the-art advances in tissue-engineered corneal substitutes: a systematic review (2020-2025)

Area of Science:

• Ophthalmology
• Biomaterials Science
• Regenerative Medicine

Background:

• Corneal blindness is a significant global health issue, with limited donor availability and complications from grafts.
• Tissue-engineered corneal substitutes offer a potential solution by restoring corneal structure and function.

Purpose of the Study:

• To systematically review advances in tissue-engineered corneal substitutes from 2020-2025.
• To classify substitutes by the corneal layer they replace and evaluate their performance and clinical potential.

Main Methods:

• A systematic review adhering to PRISMA 2020 guidelines.
• Searches conducted in PubMed, Scopus, and Web of Science for cell-based corneal substitute studies (Jan 2020-June 2025).
• Excluded keratoprostheses, acellular scaffolds, and non-cellular biomaterials.

Main Results:

• Fourteen studies included: 5 endothelial, 3 stromal, 1 epithelial, 5 epithelium-stroma.
• Endothelial substitutes showed viability and partial transparency restoration.
• Stromal substitutes achieved >80% optical transmittance and good biomechanics.
• Epithelial and multilayered substitutes demonstrated safety and feasibility in preclinical/early clinical studies.

Conclusions:

• Corneal tissue engineering has advanced, creating functional substitutes mimicking native corneal architecture.
• Limitations include small sample sizes, short follow-up, and reliance on animal models.
• Standardized clinical trials are essential for successful clinical translation.