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Gelatin-based hydrogels combined with electrical stimulation to modulate neonatal rat cardiomyocyte beating and promote maturation
Bio-Design and Manufacturing ( IF 7.9 ) Pub Date : 2020-10-09 , DOI: 10.1007/s42242-020-00100-9
Feng Zhang , Kaiyun Qu , Xiaopei Li , Chaoming Liu , Lazarus S. Ortiz , Kaihong Wu , Xiaowei Wang , Ningping Huang

Cardiovascular diseases are the leading cause of morbidity and mortality throughout the world underlining the importance of efficient treatments including disease modeling and drug discovery by cardiac tissue engineering. However, the predictive power of these applications is currently limited by the immature state of the cardiomyocytes. Here, we developed gelatin hydrogels chemically crosslinked by genipin, a biocompatible crosslinker, as cell culture scaffolds. Neonatal rat cardiomyocytes appear synchronous beating within 2 days after seeding on hydrogels. Furthermore, we applied the electrical stimulation as a conditioning treatment to promote the maturation of cardiomyocytes cultured on the hydrogels. Our results show that electrical stimulation improves the organization of sarcomeres, establishment of gap junctions, calcium-handling capacity and propagation of pacing signals, thereby, increase the beating velocity of cardiomyocytes and responsiveness to external pacing. The above system can be applied in promoting physiological function maturation of engineered cardiac tissues, exhibiting promising applications in cardiac tissue engineering and drug screening.



中文翻译:

基于明胶的水凝胶结合电刺激来调节新生大鼠心肌细胞的跳动并促进成熟

心血管疾病是全世界发病率和死亡率的主要原因,强调了有效治疗的重要性,包括疾病建模和通过心脏组织工程学发现药物。但是,这些应用的预测能力目前受到心肌细胞未成熟状态的限制。在这里,我们开发了通过生物相容性交联剂genipin化学交联的明胶水凝胶,作为细胞培养支架。新生大鼠心肌细胞植入水凝胶后2天内出现同步跳动。此外,我们应用电刺激作为调理剂,以促进水凝胶上培养的心肌细胞的成熟。我们的研究结果表明,电刺激可改善肉瘤的组织,间隙连接的建立,钙处理能力和起搏信号的传播,从而增加了心肌细胞的跳动速度和对外部起搏的反应性。上述系统可以用于促进工程心脏组织的生理功能成熟,在心脏组织工程和药物筛选中显示出有希望的应用。

更新日期:2020-10-11
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