Arterial bypass grafts remain the gold standard for the treatment of end-stage ischaemic disease. Yet patients unable to tolerate the cardiovascular stress of arterial surgery or those with unreconstructable disease would benefit from grafts that are able to induce therapeutic angiogenesis. Here, we introduce an approach whereby implantation of 3D-printed grafts containing endothelial-cell-lined lumens induces spontaneous, geometrically guided generation of collateral circulation in ischaemic settings. In rodent models of hind limb ischaemia and myocardial infarction, we demonstrate that the vascular patches rescue perfusion of distal tissues, preventing capillary loss, muscle atrophy and loss of function. Inhibiting anastomoses between the construct and the host’s local capillary beds, or implanting constructs with unpatterned endothelial cells, abrogates reperfusion. Our 3D-printed grafts constitute an efficient and scalable approach to engineer vascular patches that are able to guide rapid therapeutic angiogenesis and perfusion for the treatment of ischaemic diseases.
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We thank J. Eyckmans, R. Chaturvedi and M. Shockley for helpful discussions. This work was supported in part by grants from the National Institutes of Health (NIH; EB00262, EB08396, HL118851), the Biological Design Center of Boston University and the BU-Coulter Foundation Translational Partnership Program. D.C. was supported by the National Science Foundation. C.K.O. was supported by the American Heart Association Grant-in-Aid (16GRNT27090006). Y.J.W. was supported by NIH grant 1R01 (HL089315-01). J.W.M. was supported by the American Heart Association (12POST11620024).
C.S.C. is a cofounder of, and owns equity in, Innolign Biomedical, a company that is developing tissue-engineered products.
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Mirabella, T., MacArthur, J., Cheng, D. et al. 3D-printed vascular networks direct therapeutic angiogenesis in ischaemia. Nat Biomed Eng 1, 0083 (2017). https://doi.org/10.1038/s41551-017-0083
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