Tan Yao, Chen Ying, Lu Tingting, Witman Nevin, Yan Bingqian, Gong Yiqi, Ai Xuefeng, Yang Li, Liu Minglu, Luo Runjiao, Wang Huijing, Ministrini Stefano, Dong Wei, Wang Wei, Fu Wei
Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Front Bioeng Biotechnol. 2023 Feb 8;11:1094397. doi: 10.3389/fbioe.2023.1094397. eCollection 2023.
The healthy human heart has special directional arrangement of cardiomyocytes and a unique electrical conduction system, which is critical for the maintenance of effective contractions. The precise arrangement of cardiomyocytes (CMs) along with conduction consistency between CMs is essential for enhancing the physiological accuracy of cardiac model systems. Here, we prepared aligned electrospun rGO/PLCL membranes using electrospinning technology to mimic the natural heart structure. The physical, chemical and biocompatible properties of the membranes were rigorously tested. We next assembled human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) on electrospun rGO/PLCL membranes in order to construct a myocardial muscle patch. The conduction consistency of cardiomyocytes on the patches were carefully recorded. We found that cells cultivated on the electrospun rGO/PLCL fibers presented with an ordered and arranged structure, excellent mechanical properties, oxidation resistance and effective guidance. The addition of rGO was found to be beneficial for the maturation and synchronous electrical conductivity of hiPSC-CMs within the cardiac patch. This study verified the possibility of using conduction-consistent cardiac patches to enhance drug screening and disease modeling applications. Implementation of such a system could one day lead to cardiac repair applications.
健康的人类心脏具有心肌细胞的特殊定向排列和独特的电传导系统,这对于维持有效的收缩至关重要。心肌细胞(CMs)的精确排列以及CMs之间的传导一致性对于提高心脏模型系统的生理准确性至关重要。在这里,我们使用静电纺丝技术制备了排列整齐的电纺rGO/PLCL膜,以模拟天然心脏结构。对膜的物理、化学和生物相容性进行了严格测试。接下来,我们将人诱导多能干细胞衍生的心肌细胞(hiPSC-CMs)组装在电纺rGO/PLCL膜上,以构建心肌贴片。仔细记录了贴片上心肌细胞的传导一致性。我们发现,在电纺rGO/PLCL纤维上培养的细胞呈现出有序排列的结构、优异的机械性能、抗氧化性和有效的引导作用。发现添加rGO有利于心脏贴片中hiPSC-CMs的成熟和同步导电性。这项研究验证了使用传导一致的心脏贴片来加强药物筛选和疾病建模应用的可能性。实施这样一个系统有朝一日可能会带来心脏修复应用。