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

Authors

Mario Bonmatí-Echevarría, Carmen González-Gallardo, Miguel Alaminos

Published in

Therapeutic advances in ophthalmology. Volume 18. Pages 25158414261464536. Epub Aug 06, 2026.

Abstract

Corneal blindness remains a major global health burden, limited by donor shortage and graft-related complications. Tissue-engineered corneal substitutes have emerged as a promising alternative, aiming to restore corneal structure and function through bioengineered constructs.
To systematically review recent advances (2020-2025) in tissue-engineered corneal substitutes, classifying them according to the corneal layer replaced and evaluating their biological, optical, and functional performance, as well as their translational potential for clinical application.
A systematic review.
A systematic review was conducted following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 guidelines. Searches were performed in PubMed/MEDLINE, Scopus, and Web of Science using predefined keywords related to corneal tissue engineering. Eligible studies included experimental, preclinical, or clinical studies published between January 2020 and June 2025 describing cell-based corneal substitutes. Studies focused on keratoprostheses (KPros), acellular scaffolds, or non-cellular biomaterials were excluded.
Fourteen studies met the inclusion criteria: five endothelial, three stromal, one epithelial, and five epithelium-stroma substitutes. Endothelial models demonstrated cell viability, expression of tight junction proteins (ZO-1, Na⁺/K⁺-ATPase), and partial restoration of corneal transparency in animal and ex vivo systems. Stromal models incorporated advanced biofabrication techniques such as 3D bioprinting and neuronal co-culture, achieving > 80% optical transmittance and adequate biomechanical properties. The single epithelial model achieved complete re-epithelialization in a rabbit limbal deficiency model. Multilayered epithelium-stroma substitutes, including the NANOULCOR (Tissue Engineering Group, University of Granada, Granada, Spain) construct, exhibited safety and feasibility in preclinical and early clinical studies.
Recent progress in corneal tissue engineering has yielded increasingly functional and biocompatible substitutes that replicate native corneal architecture. However, most studies remain limited by small sample sizes, short follow-up, and reliance on animal models. Further standardized clinical trials are required for clinical translation.
Not applicable.

PMID:
42571159
Bibliographic data and abstract were imported from PubMed on 09 Aug 2026.

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