{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T08:06:34Z","timestamp":1778918794747,"version":"3.51.4"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870637"],"award-info":[{"award-number":["81870637"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32371418"],"award-info":[{"award-number":["32371418"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82301172"],"award-info":[{"award-number":["82301172"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Extensive conjunctival defects present significant clinical challenges due to limitations of current treatments including donor scarcity, immune rejection, and suboptimal graft outcomes. In this study, we developed a tissue\u2010engineered conjunctiva by integrating decellularized porcine conjunctival matrix (DPCM), human amniotic epithelial cells (hAECs), RADA16\u2010I peptide hydrogel, and a perfusion culture system. The DPCM was prepared using a phospholipase A\n                    <jats:sub>2<\/jats:sub>\n                    decellularization method and exhibited effective decellularization (93.7% DNA removal) while preserving native extracellular matrix composition. Tissue\u2010engineered constructs were fabricated by seeding hAECs suspended in 0.5% RADA16\u2010I peptide hydrogel onto DPCM scaffolds and cultured under perfusion conditions. Under perfusion culture, hAECs formed stratified cell layers with high viability (&gt;\u200990%). Compared to static culture, perfusion significantly enhanced hAEC density, distribution uniformity, and proliferation (Ki67\n                    <jats:sup>+<\/jats:sup>\n                    ), while maintaining stemness marker ABCG2 expression. After 3\u2009days, the constructs showed significant upregulation of conjunctival epithelial markers (CK4, CK13, Muc5AC) at both protein and transcriptional levels, indicating successful transdifferentiation of hAECs toward a conjunctival epithelial phenotype. This integrated approach generates a functional tissue\u2010engineered conjunctiva that promotes hAEC proliferation, stemness maintenance, and differentiation into conjunctival epithelial cells, offering a promising alternative for ocular surface reconstruction.\n                  <\/jats:p>","DOI":"10.1002\/jbm.a.70090","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T12:37:13Z","timestamp":1777466233000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reconstruction of Tissue\u2010Engineered Conjunctiva Using Human Amniotic Epithelial Cells and Decellularized Porcine Conjunctiva Matrix With\n                    <scp>RADA16<\/scp>\n                    \u2010I Peptide Hydrogel in a Perfusion Culture System"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7474-9637","authenticated-orcid":false,"given":"Dong","family":"Yuying","sequence":"first","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Jinan University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liu","family":"Jingwen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Jinan University  Guangzhou China"},{"name":"Guangzhou C\u2010MER Dennis Lam Eye Hospital  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6410-8123","authenticated-orcid":false,"given":"Chen","family":"Fangyuan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Jinan University  Guangzhou China"},{"name":"Department of Ophthalmology Guangzhou Red Cross Hospital of Jinan University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Jinan University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liu","family":"Xiaoyong","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Jinan University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wang","family":"Yingwei","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Jinan University  Guangzhou China"},{"name":"Dongguan Institute of Jinan University  Dongguan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0184-4072","authenticated-orcid":false,"given":"Chen","family":"Jian","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Jinan University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5234-6383","authenticated-orcid":false,"given":"Zhou","family":"Qing","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Jinan University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2013.10.004"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/b100002"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/jfb6041064"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.649369"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00347-022-01673-9"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18-23966"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2022.07.013"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.121.10.1369"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2019.07.018"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2017.11.054"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2019.11.006"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1088\/1748-605X\/ad08e0"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.09.014"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2009.03.003"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2022.121745"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioadv.2022.213164"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-438"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805802105"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/7906531"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.019"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2012.175"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3034"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-020-01951-w"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2023.100790"},{"issue":"12","key":"e_1_2_10_26_1","first-page":"1311","article-title":"Differentiation of Human Amniotic Epithelial Cells Into Conjunctival Epithelial\u2010Like Cells in Vitro[in Chinese]","volume":"30","author":"Zhou Q.","year":"2014","journal-title":"Chinese Journal of Cellular and Molecular Immunology"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.4238\/2015.October.29.2"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41536-020-00116-w"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0407843102"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.03.052"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2018.12.042"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/21691401.2025.2475099"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsbiomaterials.5c01129"},{"key":"e_1_2_10_34_1","article-title":"Culturing Mammalian Cells in Three\u2010Dimensional Peptide Scaffolds","volume":"136","author":"Betriu N.","year":"2018","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mtbio.2026.102900"},{"key":"e_1_2_10_36_1","article-title":"Construction of a Multilayered Mesenchymal Stem Cell Sheet With a 3D Dynamic Culture System","volume":"140","author":"Wang Y.","year":"2018","journal-title":"Journal of Visualized Experiments"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/2590536"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.07.012"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.014"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2021.05.011"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2013.11.003"},{"key":"e_1_2_10_42_1","volume-title":"Current Protocols in Stem Cell Biology","author":"Miki T.","year":"2010"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2025.05.068"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2025.07.009"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02279"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2016.04.005"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475-925X-9-70"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.35312"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.050500"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9NR04521J"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2017.08.044"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10569"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/gels8120829"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.02-0851"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2020.00753"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.3181\/0703-MR-72"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms221910528"}],"container-title":["Journal of Biomedical Materials Research Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.a.70090","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbm.a.70090","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.a.70090","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T07:08:11Z","timestamp":1778915291000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbm.a.70090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,29]]},"references-count":56,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/jbm.a.70090"],"URL":"https:\/\/doi.org\/10.1002\/jbm.a.70090","archive":["Portico"],"relation":{},"ISSN":["1549-3296","1552-4965"],"issn-type":[{"value":"1549-3296","type":"print"},{"value":"1552-4965","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,29]]},"assertion":[{"value":"2025-11-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70090"}}