Department of Aerospace and Mechanical Engineering, University of Notre Dame, 225 Multidisciplinary Research Building, Notre Dame, IN 46556.
Department of Aerospace and Mechanical Engineering, University of Notre Dame, 108B Multidisciplinary Research Building, Notre Dame, IN 46556.
J Biomech Eng. 2023 Aug 1;145(8). doi: 10.1115/1.4062736.
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.
组织工程心脏贴片作为心肌梗死再生治疗具有巨大的潜力。然而，心脏贴片与健康组织的相互作用尚未完全理解。在这里，我们研究了去细胞和细胞贴片对二维（2D）跳动心脏细胞层的影响，以及该层跳动对包裹在贴片中的细胞的影响。我们在盖玻片上培养了人诱导多能干细胞衍生的心肌细胞（iCMs），并单独使用明胶甲基丙烯酰水凝胶或包裹的 iCMs 来分别构建去细胞和细胞贴片。当将去细胞贴片放置在心脏细胞层上时，跳动特征和 Ca+2 处理特性会降低，而放置细胞贴片则会恢复这些特性。为了更好地理解由跳动的心脏细胞层引起的周期性收缩和松弛对放置在其上的贴片的影响，我们开发了一个模拟模型，计算出的应变值与实验测量的值一致。此外，这种由细胞贴片中包裹的 iCM 产生的动态培养促进了其跳动速度和频率的提高。此外，观察到包裹的 iCMs 与下面跳动的 2D iCM 层相耦合。总的来说，这项研究对去细胞/细胞贴片与跳动的 2D iCM 层的相互关系进行了详细的研究，这对于开发更先进的心脏贴片具有重要意义。
