{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T15:41:11Z","timestamp":1786722071723,"version":"build-2736575974"},"reference-count":36,"publisher":"American Chemical Society (ACS)","issue":"6","license":[{"start":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T00:00:00Z","timestamp":1716422400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T00:00:00Z","timestamp":1716422400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T00:00:00Z","timestamp":1716422400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100003052","name":"Ministry of Trade, Industry and Energy","doi-asserted-by":"publisher","award":["20003915"],"award-info":[{"award-number":["20003915"]}],"id":[{"id":"10.13039\/501100003052","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean Fund for Regenerative Medicine","award":["KFRM21A0102L1-13"],"award-info":[{"award-number":["KFRM21A0102L1-13"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,6,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Human corneal transplantation is still the only option to restore the function of corneal endothelial cells (CECs). Therefore, there is an urgent need for hCEC delivery systems to replace the human donor cornea. Here, we propose an alginate hydrogel (AH)-based delivery system, where a human fibroblast-derived, decellularized extracellular matrix (ECM) was physically integrated with AH. This AH securely combined with the ECM (ECM-AH) was approximately 50 \u03bcm thick, transparent, and permeable. The surface roughness and surface potential provided ECM-AH with a favorable microenvironment for CEC adhesion and growth in vitro. More importantly, ECM-AH could support the structural (ZO-1) and functional (Na+\/K+-ATPase) markers of hCECs, as assessed via western blotting and quantitative polymerase chain reaction, which were comparable with those of a ferritic nitrocarburizing (FNC)-coated substrate (a positive control). The cell density per unit area was also significantly better with ECM-AH than the FNC substrate at day 7. A simulation test of cell engraftment in vitro showed that hCECs were successfully transferred into the decellularized porcine corneal tissue, where they were mostly alive. Furthermore, we found out that the endothelial\u2013mesenchymal transition (EnMT)-inductive factors (Smad2 and vimentin) were largely declined with the hCECs grown on ECM-AH, whereas the EnMT inhibitory factor (Smad7) was significantly elevated. The difference was statistically significant compared to that of the FNC substrate. Moreover, we also observed that TGF-\u03b21-treated hCECs showed faster recovery of cell phenotype on the ECM. Taken together, our study demonstrates that ECM-AH is a very promising material for hCEC culture and delivery, which endows an excellent microenvironment for cell function and phenotype maintenance.<\/jats:p>","DOI":"10.1021\/acsbiomaterials.4c00040","type":"journal-article","created":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T07:02:36Z","timestamp":1716447756000},"page":"3855-3867","source":"Crossref","is-referenced-by-count":2,"title":["Alginate Hydrogel Integrated with a Human Fibroblast-Derived\nExtracellular Matrix Supports Corneal Endothelial Cell Functionality\nand Suppresses Endothelial\u2013Mesenchymal Transition"],"prefix":"10.1021","volume":"10","author":[{"given":"Euisun","family":"Song","sequence":"first","affiliation":[{"name":"Korea Institute of Science and Technology (KIST) , , ,","place":["Seoul, Republic\nof Korea, 02792"]},{"name":"KIST School, University of Science and Technology (UST) , , ,","place":["Seoul, Republic of Korea, 02792"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Won","family":"Kwon","sequence":"additional","affiliation":[{"name":"Korea Institute of Science and Technology (KIST) , , ,","place":["Seoul, Republic\nof Korea, 02792"]},{"name":"KIST School, University of Science and Technology (UST) , , ,","place":["Seoul, Republic of Korea, 02792"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choul Yong","family":"Park","sequence":"additional","affiliation":[{"name":"Dongguk University Ilsan Hospital , , ,","place":["Goyang, Republic\nof Korea, 10326"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung-Taek","family":"Kang","sequence":"additional","affiliation":[{"name":"Biotechnology Research Institute, Mgenplus Co., Ltd , ,","place":["Seoul, Republic of Korea, 06688"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8519-8316","authenticated-orcid":true,"given":"Kwideok","family":"Park","sequence":"additional","affiliation":[{"name":"Korea Institute of Science and Technology (KIST) , , ,","place":["Seoul, Republic\nof Korea, 02792"]},{"name":"KIST School, University of Science and Technology (UST) , , ,","place":["Seoul, Republic of Korea, 02792"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2024,5,23]]},"reference":[{"issue":"9","key":"2026081411102535900_cit1","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1002\/adhm.201400045","article-title":"Biodegradable\nand biocompatible poly (ethylene glycol)-based hydrogel films for\nthe regeneration of corneal endothelium","volume":"3","author":"Ozcelik","year":"2014","journal-title":"Adv.\nHealthcare Mater."},{"issue":"5","key":"2026081411102535900_cit2","doi-asserted-by":"publisher","first-page":"6594","DOI":"10.1016\/j.actbio.2013.01.020","article-title":"Ultrathin chitosan-poly (ethylene glycol) hydrogel\nfilms for corneal tissue engineering","volume":"9","author":"Ozcelik","year":"2013","journal-title":"Acta Biomater."},{"issue":"17","key":"2026081411102535900_cit3","doi-asserted-by":"publisher","first-page":"4076","DOI":"10.1016\/j.biomaterials.2010.12.034","article-title":"Human corneal endothelial\ncell growth on a silk fibroin\nmembrane","volume":"32","author":"Madden","year":"2011","journal-title":"Biomaterials"},{"issue":"9","key":"2026081411102535900_cit4","doi-asserted-by":"publisher","first-page":"3357","DOI":"10.1167\/iovs.17-21797","article-title":"Silk fibroin\nfilms for corneal endothelial regeneration: transplant in a rabbit\ndescemet membrane endothelial keratoplasty","volume":"58","author":"Va\u0301zquez","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"issue":"10","key":"2026081411102535900_cit5","doi-asserted-by":"publisher","first-page":"12116","DOI":"10.1021\/acsami.2c01709","article-title":"Novel corneal endothelial cell carrier\ncouples a biodegradable polymer and a mesenchymal stem cell-derived\nextracellular matrix","volume":"14","author":"Song","year":"2022","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"2026081411102535900_cit6","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1016\/j.colsurfb.2017.11.052","article-title":"Functionalized silk\nfibroin film scaffold using \u03b2-Carotene for cornea endothelial\ncell regeneration","volume":"164","author":"Kim","year":"2018","journal-title":"Colloids Surf., B"},{"issue":"1","key":"2026081411102535900_cit7","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.progpolymsci.2011.06.003","article-title":"Alginate: properties\nand biomedical applications","volume":"37","author":"Lee","year":"2012","journal-title":"Prog. Polym. Sci."},{"issue":"98","key":"2026081411102535900_cit8","doi-asserted-by":"publisher","first-page":"80688","DOI":"10.1039\/C5RA15376J","article-title":"Potential use of\nalginate beads as a chondrocyte delivery\nvehicle and stepwise dissolving porogen in a hydrogel scaffold for\ncartilage tissue engineering","volume":"5","author":"Fan","year":"2015","journal-title":"RSC Adv."},{"key":"2026081411102535900_cit9","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/j.biomaterials.2018.06.038","article-title":"Enzymatically\ndegradable alginate\nhydrogel systems to deliver endothelial progenitor cells for potential\nrevasculature applications","volume":"179","author":"Campbell","year":"2018","journal-title":"Biomaterials"},{"issue":"17","key":"2026081411102535900_cit10","doi-asserted-by":"publisher","first-page":"1900593","DOI":"10.1002\/adhm.201900593","article-title":"Stretchable ECM patch enhances stem\ncell delivery for post-MI cardiovascular repair","volume":"8","author":"Kim","year":"2019","journal-title":"Adv. Healthcare Mater."},{"issue":"1","key":"2026081411102535900_cit11","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1021\/acsami.6b14020","article-title":"Novel platform of cardiomyocyte culture\nand coculture via fibroblast-derived matrix-coupled aligned electrospun\nnanofiber","volume":"9","author":"Suhaeri","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"2026081411102535900_cit12","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s40135-015-0077-5","article-title":"Engineering of human\ncorneal endothelial grafts","volume":"3","author":"Zhu","year":"2015","journal-title":"Curr. Ophthalmol.\nRep."},{"issue":"3","key":"2026081411102535900_cit13","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.cbpb.2008.07.010","article-title":"Stability of reference genes for real-time PCR analyses\nin channel catfish (Ictalurus punctatus) tissues under varying physiological\nconditions","volume":"151","author":"Small","year":"2008","journal-title":"Comp. Biochem. Physiol., Part B:\nBiochem. Mol. Biol."},{"key":"2026081411102535900_cit14","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.exer.2017.10.006","article-title":"The role\nof hepatocyte\ngrowth factor in corneal wound healing","volume":"166","author":"Miyagi","year":"2018","journal-title":"Exp.\nEye Res."},{"issue":"1","key":"2026081411102535900_cit15","doi-asserted-by":"publisher","first-page":"26113","DOI":"10.1038\/srep26113","article-title":"Rho kinase inhibitor enables cell-based\ntherapy for corneal endothelial dysfunction","volume":"6","author":"Okumura","year":"2016","journal-title":"Sci. Rep."},{"issue":"11","key":"2026081411102535900_cit16","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1056\/NEJMoa1712770","article-title":"Injection of cultured\ncells with a ROCK inhibitor for bullous keratopathy","volume":"378","author":"Kinoshita","year":"2018","journal-title":"N. Engl. J. Med."},{"issue":"2","key":"2026081411102535900_cit17","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1089\/ten.tec.2015.0304","article-title":"Characterization of a novel collagen scaffold for corneal\ntissue engineering","volume":"22","author":"Zhang","year":"2016","journal-title":"Tissue Eng., Part C"},{"key":"2026081411102535900_cit18","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s13036-020-0227-7","article-title":"Alginate-based\nhydrogels as drug delivery vehicles in cancer treatment and their\napplications in wound dressing and 3D bioprinting","volume":"14","author":"Abasalizadeh","year":"2020","journal-title":"J. Biol. Eng."},{"issue":"8","key":"2026081411102535900_cit19","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1002\/mabi.200600069","article-title":"Alginate\nhydrogels as biomaterials","volume":"6","author":"Augst","year":"2006","journal-title":"Macromol. Biosci."},{"issue":"1","key":"2026081411102535900_cit20","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1021\/acs.jpcc.6b11217","article-title":"Effect\nof surface potential on the adhesion behavior of NIH3T3 cells revealed\nby quartz crystal microbalance with dissipation monitoring (QCM-D)","volume":"121","author":"Kao","year":"2017","journal-title":"J. Phys. Chem. C"},{"key":"2026081411102535900_cit21","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.colsurfb.2016.01.049","article-title":"Effect\nof surface potential on epithelial cell adhesion, proliferation and\nmorphology","volume":"141","author":"Chang","year":"2016","journal-title":"Colloids Surf., B"},{"issue":"25","key":"2026081411102535900_cit22","doi-asserted-by":"publisher","first-page":"15467","DOI":"10.1039\/D1RA02402G","article-title":"Effect of surface energy and roughness\non cell adhesion and growth-facile surface modification for enhanced\ncell culture","volume":"11","author":"Majhy","year":"2021","journal-title":"RSC Adv."},{"key":"2026081411102535900_cit23","doi-asserted-by":"publisher","first-page":"109883","DOI":"10.1016\/j.msec.2019.109883","article-title":"Surface potential and charges impact on cell responses\non biomaterials interfaces for medical applications","volume":"104","author":"Metwally","year":"2019","journal-title":"Mater. Sci. Eng., C"},{"key":"2026081411102535900_cit24","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s12929-018-0492-7","article-title":"Advances in\nculture, expansion and mechanistic studies of corneal\nendothelial cells: a systematic review","volume":"26","author":"Chen","year":"2019","journal-title":"J. Biomed.\nSci."},{"key":"2026081411102535900_cit25","volume-title":"Progress in Molecular\nBiology and Translational Science","author":"Teplow","year":"2018"},{"key":"2026081411102535900_cit26","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.actbio.2017.03.035","article-title":"Human lung fibroblast-derived matrix facilitates vascular morphogenesis\nin 3D environment and enhances skin wound healing","volume":"54","author":"Du","year":"2017","journal-title":"Acta Biomater."},{"issue":"3","key":"2026081411102535900_cit27","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/j.jcrs.2010.12.037","article-title":"Anatomy and physiology\nof the cornea","volume":"37","author":"DelMonte","year":"2011","journal-title":"J. Cataract\nRefractive Surg."},{"issue":"2","key":"2026081411102535900_cit28","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1167\/iovs.14-16166","article-title":"Understanding the process of corneal endothelial morphological\nchange in vitro","volume":"56","author":"Roy","year":"2015","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"issue":"2","key":"2026081411102535900_cit29","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.survophthal.2017.07.004","article-title":"A review of the evidence for in vivo corneal endothelial\nregeneration","volume":"63","author":"Van\nden Bogerd","year":"2018","journal-title":"Surv. Ophthalmol."},{"issue":"8","key":"2026081411102535900_cit30","doi-asserted-by":"publisher","first-page":"912","DOI":"10.1038\/sj.eye.6700559","article-title":"Biology\nof the corneal endothelium in health and disease","volume":"17","author":"Bourne","year":"2003","journal-title":"Eye"},{"key":"2026081411102535900_cit31","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1146\/annurev.cellbio.21.022404.142018","article-title":"Specificity and Versatility\nin TGF-\u03b2 Signaling\nthrough Smads","volume":"21","author":"Feng","year":"2005","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2026081411102535900_cit32","first-page":"2272","article-title":"Inhibitory effect of\nblocking TGF-\u03b2\/Smad signal on injury-induced\nfibrosis of corneal endothelium","volume":"14","author":"Sumioka","year":"2008","journal-title":"Mol. Vis."},{"key":"2026081411102535900_cit33","doi-asserted-by":"publisher","first-page":"S52","DOI":"10.1097\/ico.0b013e3181efe36a","article-title":"Endothelial mesenchymal\ntransition:\na therapeutic target in retrocorneal membrane","volume":"29","author":"Miyamoto","year":"2010","journal-title":"Cornea"},{"key":"2026081411102535900_cit34","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1152\/physrev.00021.2018","article-title":"Endothelial to mesenchymal\ntransition: role in physiology\nand in the pathogenesis of human diseases","volume":"99","author":"Piera-Velazquez","year":"2019","journal-title":"Physiol.\nRev."},{"key":"2026081411102535900_cit35","doi-asserted-by":"publisher","first-page":"S52","DOI":"10.1097\/ICO.0b013e3181efe36a","article-title":"Endothelial\nmesenchymal transition:\na therapeutic target in retrocorneal membrane","volume":"29","author":"Miyamoto","year":"2010","journal-title":"Cornea"},{"issue":"4","key":"2026081411102535900_cit36","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.stemcr.2016.09.001","article-title":"Restoration\nof corneal transparency by mesenchymal stem cells","volume":"7","author":"Mittal","year":"2016","journal-title":"Stem Cell Rep."}],"container-title":["ACS Biomaterials Science &amp; Engineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsbiomaterials.4c00040","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/abseba\/article-pdf\/10\/6\/3855\/18532645\/ab4c00040.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/abseba\/article-pdf\/10\/6\/3855\/18532645\/ab4c00040.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T15:25:37Z","timestamp":1786721137000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/abseba\/article\/10\/6\/3855\/95135\/Alginate-Hydrogel-Integrated-with-a-Human"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,23]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,5,23]]},"published-print":{"date-parts":[[2024,6,10]]}},"URL":"https:\/\/doi.org\/10.1021\/acsbiomaterials.4c00040","relation":{},"ISSN":["2373-9878"],"issn-type":[{"value":"2373-9878","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,23]]}}}