{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T08:36:52Z","timestamp":1792831012316,"version":"4.5.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:00:00Z","timestamp":1792800000000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PID2021\u2010125150OB\u2010I00"],"award-info":[{"award-number":["PID2021\u2010125150OB\u2010I00"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002809","name":"Generalitat de Catalunya","doi-asserted-by":"publisher","award":["2019PROD000053\/IU68\u2010017130"],"award-info":[{"award-number":["2019PROD000053\/IU68\u2010017130"]}],"id":[{"id":"10.13039\/501100002809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["2022 FI\u2010B1 00210"],"award-info":[{"award-number":["2022 FI\u2010B1 00210"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biomed Mater Res"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Keratoprosthesis (KPro), an artificial corneal implant, is an established surgical option for restoring vision in severe corneal blindness; however, long\u2010term outcomes remain limited by complications such as fibrosis and infection. Current biomaterial strategies generally lack the ability to address these distinct pathological processes at spatially defined implant\u2013tissue interfaces. Here, we present a modified titanium KPro backplate with spatially controlled dual\u2010functionalization, enabling spatially decoupled functionalization of opposing implant surfaces to address different biological challenges. The study was designed as an exploratory proof\u2010of\u2010concept and was not intended to determine the independent contribution or efficacy of either surface functionalization. The anterior surface was coated with antimicrobial silver nanoparticles, while the posterior surface was coated with a P17\u2010derived peptide construct designed for surface immobilization and intended to target fibrosis\u2010associated pathways. Side\u2010specific surface modification was supported by scanning electron microscopy, fluorescence microscopy, and x\u2010ray photoelectron spectroscopy. A proof\u2010of\u2010concept in\u00a0vivo study was performed in a rabbit model over 1\u2009month, comparing dual\u2010functionalized and uncoated modified KPro devices. Corneal melting occurred in 3\/6 control and 3\/5 treated eyes; among eyes with melting, the mean number of affected corneal sectors was 3 and 1, respectively. Mean graft opacification was 60% in controls and 40% in treated eyes, and mean iris adhesion was 85% in control eyes and 70% in treated. Scanning electron microscopy qualitatively showed variable amounts of ECM\u2010like fibrillar material and cellular\u2010like structures at the implant interfaces, with no consistent qualitative difference between groups. Clinical findings compatible with infection were observed in 2\/6 control eyes and 0\/5 treated eyes. These findings support the technical feasibility of spatially controlled dual\u2010functionalization and provide preliminary descriptive observations of short\u2010term tissue\u2013implant interactions during the first postoperative month, when complications are most frequent. This approach provides a basis for further evaluation of spatially programmed KPro surface engineering.<\/jats:p>","DOI":"10.1002\/jbm.b.70170","type":"journal-article","created":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T07:44:52Z","timestamp":1792827892000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spatially Controlled Dual\u2010Functionalization of a Titanium Keratoprosthesis: A Proof\u2010of\u2010Concept In\u00a0Vivo Study"],"prefix":"10.1002","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8969-8200","authenticated-orcid":false,"given":"Silvia Gonz\u00e1lez","family":"G\u00f3mez","sequence":"first","affiliation":[{"name":"Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering Universitat Polit\u00e8cnica de Catalunya. Barcelona Tech (UPC), Barcelona East School of Engineering (EEBE)  Barcelona Spain"},{"name":"Barcelona Research Center in Multiscale Science and Engineering UPC, EEBE  Barcelona Spain"},{"name":"Institut de Recerca Sant Joan de D\u00e9u  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Caballero","sequence":"additional","affiliation":[{"name":"Centro de Oftalmolog\u00eda Barraquer  Barcelona Spain"},{"name":"Institut Universitari Barraquer, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6255-2498","authenticated-orcid":false,"given":"Justin Christopher","family":"D'Antin","sequence":"additional","affiliation":[{"name":"Centro de Oftalmolog\u00eda Barraquer  Barcelona Spain"},{"name":"Institut Universitari Barraquer, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"Barraquer","sequence":"additional","affiliation":[{"name":"Centro de Oftalmolog\u00eda Barraquer  Barcelona Spain"},{"name":"Institut Universitari Barraquer, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4666-1288","authenticated-orcid":false,"given":"Gemma","family":"Julio","sequence":"additional","affiliation":[{"name":"Centro de Oftalmolog\u00eda Barraquer  Barcelona Spain"},{"name":"Institut Universitari Barraquer, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Javier","family":"Gil","sequence":"additional","affiliation":[{"name":"Bioengineering Institute of Technology Universitat Internacional de Catalunya  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Mar\u00eda","family":"Manero","sequence":"additional","affiliation":[{"name":"Biomaterials, Biomechanics and Tissue Engineering Group, Department of Materials Science and Engineering Universitat Polit\u00e8cnica de Catalunya. Barcelona Tech (UPC), Barcelona East School of Engineering (EEBE)  Barcelona Spain"},{"name":"Barcelona Research Center in Multiscale Science and Engineering UPC, EEBE  Barcelona Spain"},{"name":"Institut de Recerca Sant Joan de D\u00e9u  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2560-5922","authenticated-orcid":false,"given":"Rafael I.","family":"Barraquer","sequence":"additional","affiliation":[{"name":"Centro de Oftalmolog\u00eda Barraquer  Barcelona Spain"},{"name":"Institut Universitari Barraquer, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Universitat Internacional de Catalunya (UIC), Sant Cugat del Vall\u00e8s  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,24]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2020.09.004"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICU.0000000000000774"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICO.0000000000002883"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S219270"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oret.2018.04.010"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2012.11.019"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/09273948.2016.1269930"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00417\u2010024\u201006445\u20106"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2021.05.022"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11\u20107601"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.9.13.41"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.4c04077"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.11\u20107300"},{"issue":"5","key":"e_1_2_12_15_1","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics12050421","article-title":"Encapsulating TGF\u2010\u03b21 Inhibitory Peptides P17 and P144 as a Promising Strategy to Facilitate Their Dissolution and to Improve Their Functionalization","volume":"12","author":"Hanafy N. A. N.","year":"2020","journal-title":"Pharmaceutics"},{"issue":"6","key":"e_1_2_12_16_1","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s10856-018-6082-0","article-title":"In Vitro Cell Response on CP\u2010Ti Surfaces Functionalized With TGF\u2010\u03b21 Inhibitory Peptides","volume":"29","author":"Sevilla P.","year":"2018","journal-title":"Journal of Materials Science. Materials in Medicine"},{"issue":"3","key":"e_1_2_12_17_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.cyto.2010.11.019","article-title":"Therapeutic Effect of a Peptide Inhibitor of TGF\u2010\u03b2 on Pulmonary Fibrosis","volume":"53","author":"Arribillaga L.","year":"2011","journal-title":"Cytokine"},{"issue":"2","key":"e_1_2_12_18_1","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.cyto.2007.06.004","article-title":"Identification of Peptide Inhibitors of Transforming Growth Factor Beta 1 Using a Phage\u2010Displayed Peptide Library","volume":"39","author":"Dotor J.","year":"2007","journal-title":"Cytokine"},{"key":"e_1_2_12_19_1","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.3389\/fmicb.2016.01831","article-title":"Mechanistic Basis of Antimicrobial Actions of Silver Nanoparticles","volume":"7","author":"Dakal T. C.","year":"2016","journal-title":"Frontiers in Microbiology"},{"key":"e_1_2_12_20_1","doi-asserted-by":"crossref","DOI":"10.3389\/fbioe.2024.1421706","article-title":"Antibacterial and Cytocompatible Silver Coating for Titanium Boston Keratoprosthesis","volume":"12","author":"G\u00f3mez S. G.","year":"2024","journal-title":"Frontiers in Bioengineering and Biotechnology"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.34133\/bmr.0147"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioadv.2023.213654"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202000670"},{"issue":"3","key":"e_1_2_12_24_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.2174\/1871527315666151110124957","article-title":"Rabbit Models of Ocular Diseases: New Relevance for Classical Approaches","volume":"15","author":"Zernii E. Y.","year":"2016","journal-title":"CNS & Neurological Disorders Drug Targets"},{"issue":"5","key":"e_1_2_12_25_1","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1538\/expanim.54.395","article-title":"Spontaneous Ophthalmic Diseases in 586 New Zealand White Rabbits","volume":"54","author":"Jeong M. B.","year":"2005","journal-title":"Experimental Animals"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2025.110826"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.a.35958"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/eye.2012.136"},{"issue":"6","key":"e_1_2_12_29_1","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1097\/01.ico.0000154391.28254.1d","article-title":"Therapy of Progressive Rheumatoid Arthritis\u2010Associated Corneal Ulceration With Infliximab","volume":"24","author":"Thomas J. W.","year":"2005","journal-title":"Cornea"},{"issue":"6","key":"e_1_2_12_30_1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.3109\/09273948.2011.621580","article-title":"Clinical Features and Prognosis of Boston Type I Keratoprosthesis\u2010Associated Corneal Melt","volume":"19","author":"Utine C. A.","year":"2011","journal-title":"Ocular Immunology and Inflammation"},{"issue":"11","key":"e_1_2_12_31_1","first-page":"684","article-title":"Complications and Treatment for Deep Anterior Lamellar Keratoplasty","volume":"14","author":"Sun L.","year":"2012","journal-title":"Chinese Journal of Optometry & Ophthalmology"},{"key":"e_1_2_12_32_1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/B978-072160561-6.50014-9","volume-title":"Slatter's Fundamentals of Veterinary Ophthalmology","author":"Miller P. E.","year":"2008"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.749063"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm13226710"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1167\/tvst.9.3.20"}],"container-title":["Journal of Biomedical Materials Research Part B: Applied Biomaterials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.b.70170","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbm.b.70170","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbm.b.70170","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T07:44:54Z","timestamp":1792827894000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbm.b.70170"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":34,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/jbm.b.70170"],"URL":"https:\/\/doi.org\/10.1002\/jbm.b.70170","archive":["Portico"],"relation":{},"ISSN":["1552-4973","1552-4981"],"issn-type":[{"value":"1552-4973","type":"print"},{"value":"1552-4981","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2026-07-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-24","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70170"}}