AUTHOR=Ketabat Farinaz , Kim Andy , Alizadeh Sardroud Hamed , Eames Brian Frank , Collins Michelle , Chen Xiongbiao , Kelly Michael E. , Badea Ildiko 
  
TITLE=3D bioprinting of vascularized cardiac constructs reveals improved cardiomyocyte organization and contractile function
  
JOURNAL=Journal of Pharmacy & Pharmaceutical Sciences
  
VOLUME=Volume 29 - 2026
  
YEAR=2026
  
URL=https://www.frontierspartnerships.org/journals/journal-of-pharmacy-pharmaceutical-sciences/articles/10.3389/jpps.2026.17204
  
DOI=10.3389/jpps.2026.17204
  
ISSN=1482-1826
  
ABSTRACT=BackgroundDespite advances in cardiac tissue engineering, generating constructs that simultaneously achieve vascularization and organized cardiomyocyte function remains a major challenge.MethodsIn this study, three-dimensional (3D) bioprinting was used to fabricate human umbilical vein endothelial cell (HUVEC)-laden alginate/gelatin constructs with defined architectures designed to mimic myocardial alignment. Constructs were cultured with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) under static conditions followed by short-term dynamic stimulation in a bioreactor. Cardiomyocytes - H9c2 cells, neonatal rat ventricular myocytes (NRVMs), or human induced pluripotent stem cell–derived cardiomyocytes (iPSC-CMs) - were subsequently seeded onto the constructs. Vascularization and the distribution of cells were assessed using immunofluorescence, and functional activity of cardiomyocytes was evaluated by calcium transient imaging.ResultsBioprinted constructs developed interconnected CD31-positive endothelial networks in response to growth factor supplementation and dynamic culture, whereas control constructs cultured without growth factors or bioreactor exposure showed limited vascular organization. Cardiomyocytes seeded onto vascularized constructs exhibited improved structural organization, including increased alignment and integration with endothelial networks. Functional assessment revealed more synchronized and rhythmic calcium transients compared to non-vascularized constructs.ConclusionThis study demonstrates that combining 3D bioprinting with controlled architectural design and endothelial network formation enhances cardiomyocyte organization and function. These findings highlight the critical role of vascular-like networks in improving the performance of engineered cardiac tissues.