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Patterned human microvascular grafts enable rapid vascularization and increase perfusion in infarcted rat hearts

Meredith A. Redd, Nicole Zeinstra, Wan Qin, Wei Wei, Amy Martinson, Yuliang Wang, Ruikang K. Wang, Charles E. Murry () and Ying Zheng ()
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Meredith A. Redd: University of Washington
Nicole Zeinstra: University of Washington
Wan Qin: University of Washington
Wei Wei: University of Washington
Amy Martinson: University of Washington
Yuliang Wang: University of Washington
Ruikang K. Wang: University of Washington
Charles E. Murry: University of Washington
Ying Zheng: University of Washington

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Vascularization and efficient perfusion are long-standing challenges in cardiac tissue engineering. Here we report engineered perfusable microvascular constructs, wherein human embryonic stem cell-derived endothelial cells (hESC-ECs) are seeded both into patterned microchannels and the surrounding collagen matrix. In vitro, the hESC-ECs lining the luminal walls readily sprout and anastomose with de novo-formed endothelial tubes in the matrix under flow. When implanted on infarcted rat hearts, the perfusable microvessel grafts integrate with coronary vasculature to a greater degree than non-perfusable self-assembled constructs at 5 days post-implantation. Optical microangiography imaging reveal that perfusable grafts have 6-fold greater vascular density, 2.5-fold higher vascular velocities and >20-fold higher volumetric perfusion rates. Implantation of perfusable grafts containing additional hESC-derived cardiomyocytes show higher cardiomyocyte and vascular density. Thus, pre-patterned vascular networks enhance vascular remodeling and accelerate coronary perfusion, potentially supporting cardiac tissues after implantation. These findings should facilitate the next generation of cardiac tissue engineering design.

Date: 2019
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DOI: 10.1038/s41467-019-08388-7

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