An Experimental and Numerical Investigation of Cardiac Tissue-Patch Interrelation
An Experimental and Numerical Investigation of Cardiac Tissue-Patch Interrelation
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DOI：
10.1115/1.4062736
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发表时间：
2023-08-01
影响因子：
1.7
通讯作者：
Zorlutuna，Pinar
中科院分区：
文献类型：
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作者：
Basara，Gozde;Bahcecioglu，Gokhan;Zorlutuna，Pinar
组织工程心脏补片作为心肌梗死的再生治疗具有巨大的潜力。然而，心脏补片与健康组织的相互作用尚未完全了解。在这里，我们研究了无细胞和细胞补丁上跳动的二维（2D）心脏细胞层的影响，以及该层的跳动对包封在补丁中的细胞的影响。我们在盖玻片上培养人诱导的多能干细胞衍生的心肌细胞（iCM），并单独放置明胶甲基丙烯酰水凝胶或与包封的iCM一起分别形成无细胞和细胞贴片。当脱细胞补片放置在心脏细胞层上时，搏动特性和Ca+ 2处理特性降低，而放置细胞补片恢复了这些特性。为了更好地理解由搏动的心脏细胞层对置于其上的贴片引起的周期性收缩和松弛的影响，开发了模拟模型，并且计算的应变值与实验测量的值一致。此外，通过在包封在细胞贴片中的iCM上跳动的2D iCM层诱导的这种动态培养提高了它们的跳动速度和频率。此外，观察到包封的iCM与下面的跳动的2D iCM层偶联。总的来说，本研究提供了一个详细的调查与跳动的2D iCM层的非细胞/细胞补丁的相互关系，了解这将是有价值的开发更先进的心脏补丁。
Tissue engineered cardiac patches have great potential as a regenerative therapy for myocardial infarction. Yet, the mutual interaction of cardiac patches with healthy tissue has not been completely understood. Here, we investigated the impact of acellular and cellular patches on a beating two-dimensional (2D) cardiac cell layer, and the effect of the beating of this layer on the cells encapsulated in the patch. We cultured human-induced pluripotent stem cell-derived cardiomyocytes (iCMs) on a coverslip and placed gelatin methacryloyl hydrogel alone or with encapsulated iCMs to create acellular and cellular patches, respectively. When the acellular patch was placed on the cardiac cell layer, the beating characteristics and Ca+ 2 handling properties reduced, whereas placing the cellular patch restored these characteristics. To better understand the effects of the cyclic contraction and relaxation induced by the beating cardiac cell layer on the patch placed on top of it, a simulation model was developed, and the calculated strain values were in agreement with the values measured experimentally. Moreover, this dynamic culture induced by the beating 2D iCM layer on the iCMs encapsulated in the cellular patch improved their beating velocity and frequency. Additionally, the encapsulated iCMs were observed to be coupled with the underlying beating 2D iCM layer. Overall, this study provides a detailed investigation on the mutual relationship of acellular/cellular patches with the beating 2D iCM layer, understanding of which would be valuable for developing more advanced cardiac patches.