Gelatin-based hydrogels combined with electrical stimulation to modulate neonatal rat cardiomyocyte beating and promote
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RESEARCH ARTICLE
Gelatin-based hydrogels combined with electrical stimulation to modulate neonatal rat cardiomyocyte beating and promote maturation Feng Zhang1 · Kaiyun Qu1 · Xiaopei Li1 · Chaoming Liu1 · Lazarus S. Ortiz1 · Kaihong Wu2 · Xiaowei Wang3 · Ningping Huang1 Received: 30 June 2020 / Accepted: 19 September 2020 © Zhejiang University Press 2020
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. Keywords Gelatin hydrogel · Electrical stimulation · Cardiomyocyte maturation · Cardiac tissue engineering
Introduction Cardiovascular diseases are a major cause of death worldwide due to the very limited self-regeneration capacity of the adult heart, thus new strategies are needed for in vitro production of functional heart tissue for implantation or drug screening, or to study the development and function of heart tissue [1, 2]. Cardiac tissue engineering has led to the development Electronic supplementary material The online version of this article (https://doi.org/10.1007/s42242-020-00100-9) contains supplementary material, which is available to authorized users.
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Ningping Huang [email protected]
1
State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Si Pai Lou 2#, Nanjing 210096, China
2
Cardiovascular Center, Children’s Hospital of Nanjing Medical University, Nanjing 210008, China
3
Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
of engineered heart tissue models, intending to simulate the human heart and methods that are needed to generate the environmental signals in the developing heart [3]. In this regard, hydrogel materials have been shown to be suitable for cardiac regeneration and repair due to their ability to simulate the physical and chemical properties of native heart tissues [4, 5]. So far, several synthetic and natural hydrogels,
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