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.

Tissue engineering has offered unique opportunities for disease modeling and regenerative medicine; however, the success of these strategies is dependent on faithful reproduction of native cellular organization. Here, it is reported that ultrasound standing waves can be used to organize myoblast populations in material systems for the engineering of aligned muscle tissue constructs. Patterned muscle engineered using type I collagen hydrogels exhibits significant anisotropy in tensile strength, and under mechanical constraint, produced microscale alignment on a cell and fiber level. Moreover, acoustic patterning of myoblasts in gelatin methacryloyl hydrogels significantly enhances myofibrillogenesis and promotes the formation of muscle fibers containing aligned bundles of myotubes, with a width of 120–150 µm and a spacing of 180–220 µm. The ability to remotely pattern fibers of aligned myotubes without any material cues or complex fabrication procedures represents a significant advance in the field of muscle tissue engineering. In general, these results are the first instance of engineered cell fibers formed from the differentiation of acoustically patterned cells. It is anticipated that this versatile methodology can be applied to many complex tissue morphologies, with broader relevance for spatially organized cell cultures, organoid development, and bioelectronics.

The application of tissue engineered patches made of conductive polymer scaffolds combined with cardiomyocytes (CMs) could provide a dual method of improving the damaged myocardium after an infarction: firstly by introducing functional CMs to the area; secondly the conductive polymer could modulate electrical transmission across the scar tissue. Polyaniline (PANI) scaffolds are one such example, however, the consequences of growing CMs on conductive PANI scaffolds with regards to CM electrophysiology are unknown. In this study we assess the hypothesis that conductive PANI scaffolds affect CM calcium transients and action potential morphology in culture. Neonatal rat ventricular myocytes (NRVMs) and neonatal rat fibroblasts were co-cultured on conductive and non-conductive (sodium hydroxide treated) PANI scaffolds and remained viable after four days of culture, covering the surface of the construct. Compared to those cultured on non-conductive PANI scaffolds, NRVM cultured on conductive PANI scaffolds show faster calcium transients, measured using Fluo-4AM and field stimulated at 1 Hz, with a decrease in the time to peak (t p non-conductive=105±6 ms, t p conductive= 85±5 ms, p<0.05, n=6) and time to 50% (t 50 non-conductive=212±12 ms, t 50 conductive= 116±7 ms, p<0.001, n=6) and 90% decay (t 90 non-conductive=404±24 ms, t 90 conductive= 266±15 ms, p<0.001, n=6). Action potential morphology, assessed using FluoVolt membrane potential dye and stimulated at 1 Hz, remain unchanged for conductive and non-conductive PANI scaffolds. The PANI scaffolds are compatible with NRVMs and the cells have good viability after four days in culture. The conductive PANI scaffolds have a significant effect on myocyte calcium cycling but this is not caused by a change in action potential morphology. Further work is required to understand the mechanism behind the change in calcium handling in the CMs on the conductive PANI scaffolds.

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