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 engineer...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 beatingwithin 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.展开更多
基金This work was financially supported by the National Natural Science Foundation of China(Grant No.31871017)the Natural Science Foundation of Jiangsu Province,China(Grant No.BK20171352)+2 种基金the Southeast University-Nanjing Medical University Cooperative research project(2242019K3DN05)the Medical Science and Technology Development Foundation,Jiangsu Provincial Commission of Health and Family Planning,China(ZDRCA2016073)the“111”Project(B17011,Ministry of Education of China).
文摘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 beatingwithin 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.