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On-line Access: 2021-01-27

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Bio-Design and Manufacturing  2021 Vol.4 No.1 P.100-110

http://doi.org/10.1007/s42242-020-00100-9


Gelatin-based hydrogels combined with electrical stimulation to modulate neonatal rat cardiomyocyte beating and promote maturation


Author(s):  Feng Zhang, Kaiyun Qu, Xiaopei Li, Chaoming Liu, Lazarus S. Ortiz, Kaihong Wu, Xiaowei Wang, Ningping Huang

Affiliation(s):  State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Si Pai Lou 2#, Nanjing 210096, China; more

Corresponding email(s):   nphuang@seu.edu.cn

Key Words:  Gelatin hydrogel, Electrical stimulation, Cardiomyocyte maturation, Cardiac tissue engineering


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Feng Zhang, Kaiyun Qu, Xiaopei Li, Chaoming Liu, Lazarus S. Ortiz, Kaihong Wu, Xiaowei Wang, Ningping Huang. Gelatin-based hydrogels combined with electrical stimulation to modulate neonatal rat cardiomyocyte beating and promote maturation[J]. Journal of Zhejiang University Science D, 2021, 4(1): 100-110.

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doi="10.1007/s42242-020-00100-9"
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Abstract: 
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.

东南大学黄宁平等 | 基于明胶的水凝胶结合电刺激调节新生大鼠心肌细胞的跳动并促进成熟

本研究论文聚焦心血管疾病的治疗。心血管疾病具有高发病率、高死亡率的特点,因此,对该病的有效治疗显得尤为重要,包括通过心脏组织工程进行疾病建模和药物开发。但是,这些应用的预测能力目前受到心肌细胞不成熟状态的限制。本研究开发了通过生物相容性交联剂京尼平化学交联的明胶水凝胶,将其作为细胞培养支架,使得新生大鼠心肌细胞接种到水凝胶上后2天内出现同步跳动。此外,我们采用电刺激方法促进水凝胶上培养的心肌细胞的成熟。研究结果表明,电刺激改善了肌节的组织、间隙连接的建立、钙处理能力和起搏信号的传播,从而提高了心肌细胞跳动速度和对外部起搏的反应性。上述系统可用于促进组织工程心肌的生理功能成熟,在心脏组织工程和药物筛选方面具有广阔的应用前景。

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