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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 | Ying Zheng
Nature communications | 2019

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.

Pubmed ID: 30718840

Associated grants

  • Agency: NIH HHS, United States
    Id: P01HL094374
  • Agency: NIH HHS, United States
    Id: R01HL141570
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL128362
  • Agency: NIH HHS, United States
    Id: T32HL7312
  • Agency: NIBIB NIH HHS, United States
    Id: T32 EB001650
  • Agency: NIH HHS, United States
    Id: R01EY024158
  • Agency: NIH HHS, United States
    Id: DP2DK102258
  • Agency: NIH HHS, United States
    Id: R01HL093140
  • Agency: NIH HHS, United States
    Id: R01HL128362
  • Agency: NIH HHS, United States
    Id: P01GM081619
  • Agency: NHLBI NIH HHS, United States
    Id: R01 HL141570

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