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However, most in vitro platforms remain static. In this study, a dynamic biomaterial platform comprising a stiffening hydrogel is introduced and achieved through a stepwise approach of addition followed by light\u2010mediated crosslinking, integrated with an elastomeric substrate featuring strain\u2010responsive lamellar surface patterns. Employing this platform, the response of human induced pluripotent stem cell\u2010derived cardiomyocytes (hIPSC\u2010CMs) is investigated to dynamic stiffening from healthy to fibrotic tissue stiffness. The results demonstrate that culturing hIPSC\u2010CMs on physiologically relevant healthy stiffness significantly enhances their function, as evidenced by increased sarcomere fraction, wider sarcomere width, significantly higher connexin\u201043 content, and elevated cell beating frequency compared to cells cultured on fibrotic matrix. Conversely, dynamic matrix stiffening negatively impacts hIPSC\u2010CM function, with earlier stiffening events exerting a more pronounced hindering effect. These findings provide valuable insights into material\u2010based approaches for addressing existing challenges in hIPSC\u2010CM maturation and have broader implications across various tissue models, including muscle, tendon, nerve, and cornea, where both cellular alignment and matrix stiffening play pivotal roles in tissue development and regeneration.<\/jats:p>","DOI":"10.1002\/adhm.202402228","type":"journal-article","created":{"date-parts":[[2024,10,29]],"date-time":"2024-10-29T03:33:52Z","timestamp":1730172832000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cellular Alignment and Matrix Stiffening Induced Changes in Human Induced Pluripotent Stem Cell Derived Cardiomyocytes"],"prefix":"10.1002","volume":"14","author":[{"given":"Andrew","family":"House","sequence":"first","affiliation":[{"name":"Department of Chemical and Materials Engineering New Jersey Institute of Technology University Heights  Newark NJ 07102 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjeli","family":"Santillan","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering New Jersey Institute of Technology University Heights  Newark NJ 07102 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Correa","sequence":"additional","affiliation":[{"name":"Federated Department of Biological Sciences New Jersey Institute of Technology University Heights  Newark NJ 07102 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Youssef","sequence":"additional","affiliation":[{"name":"Federated Department of Biological Sciences New Jersey Institute of Technology University Heights  Newark NJ 07102 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3475-1051","authenticated-orcid":false,"given":"Murat","family":"Guvendiren","sequence":"additional","affiliation":[{"name":"Department of Chemical and Materials Engineering New Jersey Institute of Technology University Heights  Newark NJ 07102 USA"},{"name":"Department of Biomedical Engineering New Jersey Institute of Technology University Heights  Newark NJ 07102 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,10,29]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1116995"},{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1171643"},{"key":"e_1_2_8_1_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.06.044"},{"key":"e_1_2_8_1_4","doi-asserted-by":"publisher","DOI":"10.1016\/S0142-9612(97)00144-0"},{"key":"e_1_2_8_1_5","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(04)00075-9"},{"key":"e_1_2_8_1_6","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5317.1425"},{"key":"e_1_2_8_1_7","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903269107"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1163267"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.24.3.339"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2004.05.026"},{"key":"e_1_2_8_3_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2019.05.011"},{"key":"e_1_2_8_3_4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911642"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1063\/5.0141269"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2271"},{"key":"e_1_2_8_4_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2012.04.003"},{"key":"e_1_2_8_4_4","doi-asserted-by":"publisher","DOI":"10.1002\/anbr.202000022"},{"key":"e_1_2_8_4_5","doi-asserted-by":"publisher","DOI":"10.1002\/adma.200901055"},{"key":"e_1_2_8_4_6","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2022.1042030"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1792"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201705684"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201100821"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2010.12.006"},{"key":"e_1_2_8_6_3","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201500359"},{"key":"e_1_2_8_6_4","doi-asserted-by":"publisher","DOI":"10.1039\/C9PY01424A"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja1060615"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.200902265"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2009.10.050"},{"key":"e_1_2_8_8_3","doi-asserted-by":"publisher","DOI":"10.1557\/JMR.2005.0186"},{"key":"e_1_2_8_8_4","doi-asserted-by":"publisher","DOI":"10.1016\/j.smaim.2022.01.010"},{"key":"e_1_2_8_9_1","first-page":"4597","volume":"595","author":"Deel E. 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