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

Vascularization and efficient perfusion are long-standing challenges in cardiac tissue engineering. Here, we engineer 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. Three groups of constructs (SA only, µV only, and µV + SA) are made and cultured for three days (the same conditions as that prior to graft implantation). These constructs were then lysed for RNA collection for transcript profiling using RNAseq analysis. The microvessels in the µV only and µV + SA constructs are made from a large grid pattern (13 x 13) with lumen diameter of 125 µm to maximize the vascular surface and RNA yield. Each group had duplicate samples.