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  • 1
    In: Journal of Applied Physics, AIP Publishing, Vol. 134, No. 5 ( 2023-08-07)
    Abstract: The occurrence of atrial fibrillation (AF), one of the most socially significant arrhythmias, is associated with the presence of areas of fibrosis. Fibrosis introduces conduction heterogeneity into the cardiac tissue and, thus, may be a substrate for spiral wave reentry, which provokes the onset of AF and is often associated with its persistence. Despite results from computer and animal models of cardiac tissues, data on the conditions under which microreentries occur in human tissues are limited. In this work, we conducted a study of the new approach to modeling the fibrous atrial tissue, which takes into account the cellular structure and conduction in fibrosis areas. Using the Potts model, we created a realistic texture of atrial tissues remodeled by fibroblasts and showed the presence of pathways in such a system with a low proportion of fibroblasts. Our study revealed the relationship between the shape of the cells’ action potential, their location in the tissue, and the direction of the wave propagation. The wavefront obtained in the model creates a dynamic heterogeneity of the tissue, which affects the migration and pinning of spiral waves, and explains the formation of microreentries in the cardiac tissue. In the future, such a model can become a potential tool for predictive modeling of AF and the search for ablation target identification.
    Type of Medium: Online Resource
    ISSN: 0021-8979 , 1089-7550
    Language: English
    Publisher: AIP Publishing
    Publication Date: 2023
    detail.hit.zdb_id: 220641-9
    detail.hit.zdb_id: 3112-4
    detail.hit.zdb_id: 1476463-5
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  • 2
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 24, No. 12 ( 2023-06-20), p. 10406-
    Abstract: Myocardial remodeling is an inevitable risk factor for cardiac arrhythmias and can potentially be corrected with cell therapy. Although the generation of cardiac cells ex vivo is possible, specific approaches to cell replacement therapy remain unclear. On the one hand, adhesive myocyte cells must be viable and conjugated with the electromechanical syncytium of the recipient tissue, which is unattainable without an external scaffold substrate. On the other hand, the outer scaffold may hinder cell delivery, for example, making intramyocardial injection difficult. To resolve this contradiction, we developed molecular vehicles that combine a wrapped (rather than outer) polymer scaffold that is enveloped by the cell and provides excitability restoration (lost when cells were harvested) before engraftment. It also provides a coating with human fibronectin, which initiates the process of graft adhesion into the recipient tissue and can carry fluorescent markers for the external control of the non-invasive cell position. In this work, we used a type of scaffold that allowed us to use the advantages of a scaffold-free cell suspension for cell delivery. Fragmented nanofibers (0.85 µm ± 0.18 µm in diameter) with fluorescent labels were used, with solitary cells seeded on them. Cell implantation experiments were performed in vivo. The proposed molecular vehicles made it possible to establish rapid (30 min) electromechanical contact between excitable grafts and the recipient heart. Excitable grafts were visualized with optical mapping on a rat heart with Langendorff perfusion at a 0.72 ± 0.32 Hz heart rate. Thus, the pre-restored grafts’ excitability (with the help of a wrapped polymer scaffold) allowed rapid electromechanical coupling with the recipient tissue. This information could provide a basis for the reduction of engraftment arrhythmias in the first days after cell therapy.
    Type of Medium: Online Resource
    ISSN: 1422-0067
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 3
    In: Micromachines, MDPI AG, Vol. 14, No. 1 ( 2022-12-25), p. 51-
    Abstract: Induced pluripotent stem cells (iPSCs) constitute a potential source of patient-specific human cardiomyocytes for a cardiac cell replacement therapy via intramyocardial injections, providing a major benefit over other cell sources in terms of immune rejection. However, intramyocardial injection of the cardiomyocytes has substantial challenges related to cell survival and electrophysiological coupling with recipient tissue. Current methods of manipulating cell suspensions do not allow one to control the processes of adhesion of injected cells to the tissue and electrophysiological coupling with surrounding cells. In this article, we documented the possibility of influencing these processes using polymer kernels: biocompatible fiber fragments of subcellular size that can be adsorbed to a cell, thereby creating the minimum necessary adhesion foci to shape the cell and provide support for the organization of the cytoskeleton and the contractile apparatus prior to adhesion to the recipient tissue. Using optical excitation markers, the restoration of the excitability of cardiomyocytes in suspension upon adsorption of polymer kernels was shown. It increased the likelihood of the formation of a stable electrophysiological coupling in vitro. The obtained results may be considered as a proof of concept that the stochastic engraftment process of injected suspension cells can be controlled by smart biomaterials.
    Type of Medium: Online Resource
    ISSN: 2072-666X
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2620864-7
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