{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T15:41:11Z","timestamp":1786290071931,"version":"build-2736575974"},"reference-count":26,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS PI23\/00335"],"award-info":[{"award-number":["FIS PI23\/00335"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["ICI21\/00010"],"award-info":[{"award-number":["ICI21\/00010"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014440","name":"Ministry of Science, Innovation and Universities","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100014440","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ophthalmol Eye Dis"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>To systematically review recent advances (2020\u20132025) 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>A systematic review.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources and methods:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Fourteen studies met the inclusion criteria: five endothelial, three stromal, one epithelial, and five epithelium\u2013stroma substitutes. Endothelial models demonstrated cell viability, expression of tight junction proteins (ZO-1, Na\n                      <jats:sup>+<\/jats:sup>\n                      \/K\n                      <jats:sup>+<\/jats:sup>\n                      -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\u2009&gt;\u200980% optical transmittance and adequate biomechanical properties. The single epithelial model achieved complete re-epithelialization in a rabbit limbal deficiency model. Multilayered epithelium\u2013stroma substitutes, including the NANOULCOR (Tissue Engineering Group, University of Granada, Granada, Spain) construct, exhibited safety and feasibility in preclinical and early clinical studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/25158414261464536","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T06:35:24Z","timestamp":1786084524000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["State-of-the-art advances in tissue-engineered corneal substitutes: a systematic review (2020\u20132025)"],"prefix":"10.1177","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6482-2284","authenticated-orcid":false,"given":"Mario","family":"Bonmat\u00ed-Echevarr\u00eda","sequence":"first","affiliation":[{"name":"Division of Ophthalmology, University Hospital Cl\u00ednico San Cecilio, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Gonz\u00e1lez-Gallardo","sequence":"additional","affiliation":[{"name":"Division of Ophthalmology, University Hospital Cl\u00ednico San Cecilio, Granada, Spain"},{"name":"Department of Histology, Tissue Engineering Group, School of Medicine, University of Granada, Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Alaminos","sequence":"additional","affiliation":[{"name":"Department of Histology, Tissue Engineering Group, School of Medicine, University of Granada, Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.4103\/ijo.IJO_646_17"},{"key":"e_1_3_4_3_2","first-page":"789491","article-title":"Artificial cornea: past, current, and future directions","volume":"8","author":"Holland G","year":"2021","unstructured":"Holland G, Pandit A, S\u00e1nchez-Abella L, et al. 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Infectious keratitis: an update on epidemiology, causative microorganisms, risk factors, and antimicrobial resistance. Eye (Lond) 2021; 35(4): 1084\u2013101.","journal-title":"Eye (Lond)"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-016487"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/aos.15292"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.119.4.484"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114612"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-024-03759-4"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","unstructured":"Page MJ McKenzie JE Bossuyt PM et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. 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