Date Published: April 16, 2018
Author(s): Michaella Kapnisi, Catherine Mansfield, Camille Marijon, Anne Geraldine Guex, Filippo Perbellini, Ifigeneia Bardi, Eleanor J. Humphrey, Jennifer L. Puetzer, Damia Mawad, Demosthenes C. Koutsogeorgis, Daniel J. Stuckey, Cesare M. Terracciano, Sian E. Harding, Molly M. Stevens.
An auxetic conductive cardiac patch (AuxCP) for the treatment of myocardial infarction (MI) is introduced. The auxetic design gives the patch a negative Poisson’s ratio, providing it with the ability to conform to the demanding mechanics of the heart. The conductivity allows the patch to interface with electroresponsive tissues such as the heart. Excimer laser microablation is used to micropattern a re-entrant honeycomb (bow-tie) design into a chitosan-polyaniline composite. It is shown that the bow-tie design can produce patches with a wide range in mechanical strength and anisotropy, which can be tuned to match native heart tissue. Further, the auxetic patches are conductive and cytocompatible with murine neonatal cardiomyocytes in vitro. Ex vivo studies demonstrate that the auxetic patches have no detrimental effect on the electrophysiology of both healthy and MI rat hearts and conform better to native heart movements than unpatterned patches of the same material. Finally, the AuxCP applied in a rat MI model results in no detrimental effect on cardiac function and negligible fibrotic response after two weeks in vivo. This approach represents a versatile and robust platform for cardiac biomaterial design and could therefore lead to a promising treatment for MI.
Cardiovascular diseases (CVDs) are the leading causes of death and disability worldwide. Biomaterials and regenerative therapies represent exciting possible solutions.[2–8] Herein, we investigate a new biomaterial design for cardiac patches to treat myocardial infarction (MI), one of the largest contributors to CVDs. MI are caused by an occlusion of one or more of the coronary arteries, resulting in the myocardial tissue becoming ischemic and reducing the heart’s ability to pump blood around the body. Cardiac patches seek to strengthen the tissue, supply cells or growth factors to vitalize the tissue, and bridge electrical and/or mechanical stimulation across the infarct to maintain and improve cardiac function. For a cardiac patch to be successful in triggering regeneration of the myocardium, the biomaterial design will benefit from considering and optimizing the cytocompatibility, electrical conductivity, and mechanical properties.[2–8]
We can create auxetic micropatterned cardiac patches by excimer laser microablation with mechanical properties tuned to match those of native heart tissue while maintaining the bulk properties of the material. We showed that the AuxCPs are conductive (≈10−2 S cm−1) and cytocompatible with cardiomyocytes. Ex vivo experiments demonstrated that the AuxCPs have no detrimental effect on the cardiac electrophysiology of both healthy and MI hearts. Further new ex vivo experiments showed that the AuxCPs stretch and conform to match the movements of native heart tissue, unlike the UnpatCPs. Finally, the AuxCPs integrated with native heart tissue without detrimental effect on cardiac function in a rat MI model over two weeks in vivo.
Extended experimental descriptions can be found in the Supporting Information.
Supporting Information is available from the Wiley Online Library or from the author.