Abstract
Cardiac patches can help to restore the electrophysiological properties of the heart after myocardial infarction. However, scaffolds for the repair of heart muscle typically require surgical implantation or, if they are injectable, they are not electrically conductive or do not maintain their shape or function. Here, we report the performance, as demonstrated for the repair of infarcted heart muscle in rats and minipigs, of injectable and conductive scaffolds consisting of methacrylated elastin and gelatin, and carbon nanotubes that display shape-memory behaviour, a hierarchical porous structure and a negligible Poisson’s ratio. In rats, the implantation of cell-free patches or patches seeded with rat cardiomyocytes onto the myocardium after ligation of the left anterior descending coronary artery led to functional repair after 4 weeks, as indicated by increases in fractional shortening and the ejection fraction, and by a decrease in the infarcted area. We also observed measures of functional recovery in minipigs with infarcted hearts after the delivery of cell-free patches or patches incorporating cardiomyocytes differentiated from human pluripotent stem cells.
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Data availability
The main data supporting the results in this study are available within the paper and its Supplementary Information. The raw and analysed datasets generated during the study are too large to be publicly shared, yet they are available for research purposes from the corresponding authors on reasonable request.
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Acknowledgements
This research was supported by the National Natural Science Foundation of China (nos U1601221, 31922043 and 31572343), Guangdong Province Science and Technology Projects (2016B090913004). M.M.Q.X. and K.M thank NSERC Discovery grants and NSERC Discovery Accelerator Supplements (DAS) Awards for supporting this work.
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Contributions
M.M.Q.X. and X.Q. conceived the research. X.Q. and M.M.Q.X. supervised the project and provided research direction, including all experimental designs. Y.L., M.M.Q.X. and L.W. synthesized and characterized the materials. L.W., Y.L., X.Q., M.M.Q.X., B.L., G.Y. and Y.H. performed the in vitro experiments of the engineered cardiac patches. L.W., G.Y., Y.H., Y.G., B.G. and X.Q. performed the in vivo experiments. K.M. provided critical input that shaped the research, data analysis and manuscript revision. L.W., Y.L., X.Q. and M.M.Q.X. verified data integrity and performed the statistical analyses. M.M.Q.X., L.W., Y.L., K.M., B.L. and X.Q. interpreted the data and co-wrote the manuscript. All of the authors reviewed the manuscript.
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Peer review information Nature Biomedical Engineering thanks Milica Radisic and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Supplementary information
Supplementary Information
Supplementary Figs. 1–23, Tables 1–17 and References, and the captions for Supplementary Videos 1–10.
Supplementary Video 1
Rigid CNTs bridged by extremely flexible biomacromolecular coils.
Supplementary Video 2
The compressive elasticity and water-driven shape memory behaviour of the EGC20 scaffold.
Supplementary Video 3
The loading, injection and instant-recovery process of an EGC20 patch injected out of the pipette tip.
Supplementary Video 4
Minimally invasive delivery of an EGC20 patch onto porcine heart through a catheter.
Supplementary Video 5
Fibrin-glue delivery under a simulative thoracoscope trainer.
Supplementary Video 6
Calcium transients in rat CMs cultured in different scaffolds on day 7.
Supplementary Video 7
Synchronous contraction of an EGC20 cardiac patch seeded with rat cardiomyocytes in vitro on day 7.
Supplementary Video 8
HECP injected and fixed on the infarcted heart of a porcine MI model.
Supplementary Video 9
LV at the papillary-muscle level in the study groups, captured by echocardiography.
Supplementary Video 10
Beating activity of hPSC-differentiated cardiomyocytes.
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Wang, L., Liu, Y., Ye, G. et al. Injectable and conductive cardiac patches repair infarcted myocardium in rats and minipigs. Nat Biomed Eng 5, 1157–1173 (2021). https://doi.org/10.1038/s41551-021-00796-9
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DOI: https://doi.org/10.1038/s41551-021-00796-9
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