{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T04:59:32Z","timestamp":1792558772212,"version":"4.5.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"19","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,5,13]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Inducing the growth of new blood vessels by specific factors is an attractive strategy to restore blood flow in ischemic tissues. Vascular endothelial growth factor (VEGF) is the master regulator of angiogenesis, yet clinical trials of VEGF gene delivery failed. Major challenges include the need to control the tissue distribution of factor dose and the duration of expression. Here, we developed a highly tunable fibrin-based platform to precisely control the dose and duration of VEGF protein delivery in tissues. Optimized delivery of fibrin-bound VEGF ensured normal, stable, and functional angiogenesis and improved perfusion of ischemic tissues, without genetic modification and with limited duration of VEGF delivery. These findings suggest a strategy to improve both safety and efficacy of therapeutic angiogenesis.<\/jats:p>","DOI":"10.1073\/pnas.1404605111","type":"journal-article","created":{"date-parts":[[2014,4,29]],"date-time":"2014-04-29T03:37:37Z","timestamp":1398742657000},"page":"6952-6957","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":151,"title":["Long-lasting fibrin matrices ensure stable and functional angiogenesis by highly tunable, sustained delivery of recombinant VEGF\n                    <sub>164<\/sub>"],"prefix":"10.1073","volume":"111","author":[{"given":"Veronica","family":"Sacchi","sequence":"first","affiliation":[{"name":"Cell and Gene Therapy, Department of Biomedicine, University of Basel, and Department of Surgery, Basel University Hospital, CH-4031 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Mittermayr","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Allgemeine Unfallversicherungsanstalt, A-1200 Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim","family":"Hartinger","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Allgemeine Unfallversicherungsanstalt, A-1200 Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika\u00ebl M.","family":"Martino","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne, CH-1015 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen M.","family":"Lorentz","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne, CH-1015 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Wolbank","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Allgemeine Unfallversicherungsanstalt, A-1200 Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Allgemeine Unfallversicherungsanstalt, A-1200 Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remo A.","family":"Largo","sequence":"additional","affiliation":[{"name":"Departments of dUrology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey S.","family":"Marschall","sequence":"additional","affiliation":[{"name":"Obstetrics, Zurich University Hospital, CH-8091 Zurich, Switzerland; and"},{"name":"University of Louisville School of Dentistry, Louisville, KY 40202"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Groppa","sequence":"additional","affiliation":[{"name":"Cell and Gene Therapy, Department of Biomedicine, University of Basel, and Department of Surgery, Basel University Hospital, CH-4031 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Gianni-Barrera","sequence":"additional","affiliation":[{"name":"Cell and Gene Therapy, Department of Biomedicine, University of Basel, and Department of Surgery, Basel University Hospital, CH-4031 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Ehrbar","sequence":"additional","affiliation":[{"name":"Obstetrics, Zurich University Hospital, CH-8091 Zurich, Switzerland; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey A.","family":"Hubbell","sequence":"additional","affiliation":[{"name":"Institute of Bioengineering, School of Life Sciences and School of Engineering, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne, CH-1015 Lausanne, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Redl","sequence":"additional","affiliation":[{"name":"Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Allgemeine Unfallversicherungsanstalt, A-1200 Vienna, Austria;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Banfi","sequence":"additional","affiliation":[{"name":"Cell and Gene Therapy, Department of Biomedicine, University of Basel, and Department of Surgery, Basel University Hospital, CH-4031 Basel, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2014,4,28]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.543124"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2895"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10144"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.200386"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2004.09.001"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2010.01.004"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI18420"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.4.12.1317"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.8.1939"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp152"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.200900241"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-005-0011-7"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2008.0527"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/74473"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/bc9800769"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000126411.29641.08"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/bit.20168"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2011.09.088"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.04.050"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2007.12.002"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.08.109"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.07.001"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000019540.41697.60"},{"key":"e_1_3_3_24_2","first-page":"1667","article-title":"Mouse model of angiogenesis","volume":"152","author":"Couffinhal T","year":"1998","unstructured":"T Couffinhal, et al., Mouse model of angiogenesis. Am J Pathol 152, 1667\u20131679 (1998).","journal-title":"Am J Pathol"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64062-X"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-0016(03)00010-8"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07424"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1089\/hgtb.2012.197"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-6568fje"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehq433"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1001\/archsurg.134.2.200"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-3659(01)00266-8"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524-475X.2007.00238.x"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1404605111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T22:39:57Z","timestamp":1649803197000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1404605111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,28]]},"references-count":33,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2014,5,13]]}},"alternative-id":["10.1073\/pnas.1404605111"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1404605111","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,28]]},"assertion":[{"value":"2014-04-28","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}