Journal
ADVANCED HEALTHCARE MATERIALS
Volume 7, Issue 23, Pages -Publisher
WILEY
DOI: 10.1002/adhm.201800672
Keywords
bioprinting; cardiac extracellular matrix; cardiac patches; cardiac progenitor cells; pediatric heart failure
Funding
- Betkowsi Family Research Fund
- NHLBI [R01HL113468]
- Cell and Tissue Engineering NIH Biotechnology Training Grant [T32 GM008433]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL113468] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008433] Funding Source: NIH RePORTER
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Congenital heart defects are present in 8 of 1000 newborns and palliative surgical therapy has increased survival. Despite improved outcomes, many children develop reduced cardiac function and heart failure requiring transplantation. Human cardiac progenitor cell (hCPC) therapy has potential to repair the pediatric myocardium through release of reparative factors, but therapy suffers from limited hCPC retention and functionality. Decellularized cardiac extracellular matrix hydrogel (cECM) improves heart function in animals, and human trials are ongoing. In the present study, a 3D-bioprinted patch containing cECM for delivery of pediatric hCPCs is developed. Cardiac patches are printed with bioinks composed of cECM, hCPCs, and gelatin methacrylate (GelMA). GelMA-cECM bioinks print uniformly with a homogeneous distribution of cECM and hCPCs. hCPCs maintain >75% viability and incorporation of cECM within patches results in a 30-fold increase in cardiogenic gene expression of hCPCs compared to hCPCs grown in pure GelMA patches. Conditioned media from GelMA-cECM patches show increased angiogenic potential (>2-fold) over GelMA alone, as seen by improved endothelial cell tube formation. Finally, patches are retained on rat hearts and show vascularization over 14 d in vivo. This work shows the successful bioprinting and implementation of cECM-hCPC patches for potential use in repairing damaged myocardium.
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