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

Nat Commun. 2019 Feb 4;10(1):584. doi: 10.1038/s41467-019-08388-7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Heart / physiology*
  • Humans
  • Male
  • Microvessels / cytology
  • Microvessels / metabolism
  • Myocardial Infarction / metabolism*
  • Myocytes, Cardiac / metabolism*
  • Neovascularization, Pathologic
  • Neovascularization, Physiologic
  • Rats
  • Rats, Nude
  • Rats, Sprague-Dawley
  • Tissue Engineering / methods