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3D-printed vascular networks direct therapeutic angiogenesis in ischaemia

Nature Biomedical Engineering volume 1, Article number: 0083 (2017) Cite this article

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An Author Correction to this article was published on 06 April 2020

Abstract

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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Figure 1: Fabricated VPs rescue perfusion in hind limb ischaemia.
Figure 2: Host-driven biointegration of grafts drives perfusion of ischaemic limb.
Figure 3: Geometric patterning within VPs impacts perfusion performance.
Figure 4: Fabricated VPs rescue cardiac function after MI in rats.

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Acknowledgements

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).

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Authors and Affiliations

  1. Department of Bioengineering and the Biological Design Center, Boston University, Boston, Massachusetts 02215, USA

    T. Mirabella, D. Cheng & C. S. Chen

  2. The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, USA

    T. Mirabella, D. Cheng & C. S. Chen

  3. Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA

    J. W. MacArthur

  4. Department of Surgery, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA

    C. K. Ozaki

  5. Department of Cardiothoracic Surgery, Stanford University, Palo Alto, California 94305, USA

    Y. J. Woo

  6. Innolign Biomedical, Boston, Massachusetts 02215, USA

    M. T. Yang

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Contributions

T.M., J.W.M., D.C., C.K.O., Y.J.W., M.T.Y. and C.S.C. conceived, developed and mentored the project. T.M., J.W.M., D.C. and M.T.Y. performed the experiments. T.M. and J.W.M, analysed the data. T.M. and C.S.C. wrote the manuscript.

Corresponding author

Correspondence to C. S. Chen.

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Competing interests

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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