Olivia Prado, Sherina Malkani, Fredrik Johansson, Fan Zhang, Arafat Fasuyi, Sarah H Saxton, Ian S Kinstlinger, Jordan S Miller, Kelly R Stevens
Engineered tissues could one day offer critical therapeutic relief for those requiring whole organ transplantation. Yet, their translation remains hindered by the need for robust vascularization throughout tissues of organ-scale sizes. Here, we used selective laser sintering of sacrificial isomalt templates to pattern vascular-promoting "tracks" across murine organ-scale tissue constructs. Upon implantation in mice, the patterned tracks architecturally guided host-mediated vascularization within fibrin and gelatin methacrylate/methacryloyl (GelMA) constructs. While the inclusion of tracks improved the vascularization response within both matrices, GelMA constructs demonstrated greater implant stability after 1 week in vivo. Subsequent implantation of GelMA constructs that were densely cellularized generated widespread, volumetric circulatory integration via both track-guided and self-assembled new blood vessels. This platform enables the generation of vascular networks spanning large, engineered tissues that can fully integrate with host circulation and represents a significant step toward the development of clinically translatable organ-scale tissues.