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Human induced pluripotent stem cell\u2010derived cardiomyocytes (hiPSC\u2010CMs) offer a promising route forward, but conventional 2D culture on rigid substrates hinders their functional maturation and predictive accuracy. This study addresses this problem by investigating the effect of hybrid fibronectin\u2010based hydrogels with tunable stiffness on the mechanical and electrical properties of hiPSC\u2010CMs. We engineered hydrogels with stiffness mimicking the lowest range of neonatal heart tissue stiffness (2\u20134 kPa) and compared hiPSC\u2010CM behavior on these substrates to that on standard fibronectin\u2010coated glass. Our results demonstrate that hydrogel culture promotes more uniform and stable cardiomyocyte contractions, as evidenced by increased single peak percentages and altered contraction duration. Electrophysiological analysis revealed that hydrogel stiffness influences action potential duration and signal amplitude. Furthermore, hiPSC\u2010CMs on hydrogels exhibited enhanced cell\u2010matrix and cell\u2013cell adhesion, indicating improved structural and functional connectivity. Drug testing with known cardioactive compounds, including isoproterenol and nifedipine, revealed distinct differences in drug responses between hydrogel and glass cultures, suggesting that hydrogels provide a more physiologically relevant platform for assessing drug effects. This work highlights the potential of engineered hydrogel substrates to enhance the functional maturity and predictive accuracy of hiPSC\u2010CMs for cardiac research and drug development.<\/jats:p>","DOI":"10.1002\/adhm.202501595","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T09:51:49Z","timestamp":1764409909000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanical and Electrical Phenotype of hiPSC\u2010Cardiomyocytes on Fibronectin\u2010Based Hydrogels"],"prefix":"10.1002","volume":"15","author":[{"given":"Ana Da Silva","family":"Costa","sequence":"first","affiliation":[{"name":"School of Cardiovascular and Metabolic Health University of Glasgow  Glasgow UK"},{"name":"MVLS Graduate School University of Glasgow  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lineta","family":"Stonkute","sequence":"additional","affiliation":[{"name":"MVLS 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