We report the fabrication of a scaffold (hereafter referred to as AngioChip) that supports the assembly of parenchymal cells on a mechanically tunable matrix surrounding a perfusable, branched, three-dimensional microchannel network coated with endothelial cells. The design of AngioChip decouples the material choices for the engineered vessel network and for cell seeding in the parenchyma, enabling extensive remodelling while maintaining an open-vessel lumen. The incorporation of nanopores and micro-holes in the vessel walls enhances permeability, and permits intercellular crosstalk and extravasation of monocytes and endothelial cells on biomolecular stimulation. We also show that vascularized hepatic tissues and cardiac tissues engineered by using AngioChips process clinically relevant drugs delivered through the vasculature, and that millimetre-thick cardiac tissues can be engineered in a scalable manner. Moreover, we demonstrate that AngioChip cardiac tissues implanted with direct surgical anastomosis to the femoral vessels of rat hindlimbs establish immediate blood perfusion.
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We thank K. Marjan and P. Lai from the University Health Network, Toronto, for their help in the optical mapping analysis. We thank Y. Liu from Osaka University, Japan, for her help in quantifying the platelet coverage on the AngioChip in the blood perfusion study. We thank J. W. Miklas and Y. Xiao for their helpful discussion regarding human cardiomyocyte culture and cell seeding. We thank A. Sofla for his help with the POMaC synthesis. We thank A. Keating and I. Rashedi for providing hMSCs and Y. Zhao for her help in culturing and expanding hMSCs. We thank J. Yang for suggestions regarding POMaC synthesis. This work was made possible by the National Sciences and Engineering Research Council of Canada (NSERC) Steacie Fellowship to M.R. This work was also financially supported by the Canadian Institutes of Health Research (CIHR) Operating Grants (MOP-126027 and MOP-137107), the Heart and Stroke Foundation GIA T6946, NSERC–CIHR Collaborative Health Research Grant (CHRPJ 385981-10), NSERC Discovery Grant (RGPIN 326982-10), NSERC Discovery Accelerator Supplement (RGPAS 396125-10) and National Institutes of Health Grant 2R01 HL076485.
M.R. and B.Z. are amongst co-founders of TARA Biosystems and they hold equity in this company.
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Zhang, B., Montgomery, M., Chamberlain, M. et al. Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis. Nature Mater 15, 669–678 (2016). https://doi.org/10.1038/nmat4570
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