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The morphogenesis of these cells to form a network is intricately regulated by the mechanical and biochemical properties of the extracellular matrix. Here the effects of modulating these properties in hydrogels derived from phenolated hyaluronic acid (HA\u2010Ph) and phenolated gelatin (Gelatin\u2010Ph) are presented. Visible\u2010light irradiation in the presence of tris(2,2\u2032\u2010bipyridyl)ruthenium(II) chloride hexahydrate and sodium persulfate induces the crosslinking of these polymers, thereby forming a hydrogel and degrading HA\u2010Ph. Human vascular endothelial cells form networks on the hydrogel prepared by visible\u2010light irradiation for 45\u00a0min (42\u00a0W cm<jats:sup>\u22122<\/jats:sup> at 450\u00a0nm) but not on the hydrogels prepared by irradiation for 15, 30, or 60\u00a0min. The irradiation time\u2010dependent degradation of HA\u2010Ph and the changes in the mechanical stiffness of the hydrogels, coupled with the expressions of RhoA and \u03b2\u2010actin genes and CD44 receptors in the cells, reveal that the network formation is synergistically influenced by the hydrogel stiffness and HA\u2010Ph degradation. These findings highlight the potential of tailoring HA\u2010based hydrogel properties to modulate human vascular endothelial cell responses, which is critical for advancing their application in vascular tissue engineering.<\/jats:p>","DOI":"10.1002\/adhm.202303787","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T17:28:26Z","timestamp":1714411706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Phototuning of Hyaluronic\u2010Acid\u2010Based Hydrogel Properties to Control Network Formation in Human Vascular Endothelial Cells"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9649-0635","authenticated-orcid":false,"given":"Kelum Chamara Manoj Lakmal","family":"Elvitigala","sequence":"first","affiliation":[{"name":"Department of Materials Engineering Science Graduate School of Engineering Science Osaka University  Toyonaka Osaka 560\u20108531 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Mohan","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Henry Samueli School of Engineering University of California Los Angeles  Los Angeles CA 90095 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2545-1206","authenticated-orcid":false,"given":"Wildan","family":"Mubarok","sequence":"additional","affiliation":[{"name":"Department of Materials Engineering Science Graduate School of Engineering Science Osaka University  Toyonaka Osaka 560\u20108531 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1041-4798","authenticated-orcid":false,"given":"Shinji","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Materials Engineering Science Graduate School of Engineering Science Osaka University  Toyonaka Osaka 560\u20108531 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,6]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.107.4.1589"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2014.05.006"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2013.01.030"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/gels9020155"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2022.08.175"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcis.2023.09.183"},{"key":"e_1_2_8_7_1","volume":"15","author":"Fan F.","year":"2023","journal-title":"ACS Appl. 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