Department of Finemechanics, Tohoku University, 6-6-1 Aramaki Aoba, Sendai, 980-8579, Japan.
Macromol Biosci. 2019 Jun;19(6):e1900060. doi: 10.1002/mabi.201900060. Epub 2019 Apr 30.
A hydrogel-based microchamber with organic electrodes for efficient electrical stimulations of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is described. The microchamber is made from molecularly permeable, optically transparent, and electrically conductive polyvinyl alcohol (PVA) hydrogel and highly capacitive carbon electrode modified with poly(3,4-ethylenedioxythiophene) (PEDOT). Spheroids of hiPSC-CMs are cultured in microchambers, and electrically stimulated by the electrode for maturation. The large interfacial capacitance of the electrodes enables several days of electrical stimulation without generation of cytotoxic bubbles even when the electrodes are placed near the spheroids. The spheroids can be cultivated in the closed microchambers because of the permeated nutrients through the hydrogel, thus the spheroids are stably addressable and the culture medium around the sealed microchambers can be simply exchanged. Synchronized beating of the spheroids can be optically analyzed in situ, which makes it possible to selectively collect electrically responsive cells for further use. As the hydrogel is electrically conductive, the amount of electrical charge needed for maturing the spheroids can be reduced by configuring electrodes on the top and the bottom of the microchamber. The bioreactor will be useful for efficient production of matured hiPSC-CMs for regenerative medicine and drug screening.
一种基于水凝胶的微腔室，带有有机电极，可有效刺激人诱导多能干细胞衍生的心肌细胞（hiPSC-CMs）。该微腔室由分子可渗透、光学透明且导电的聚乙烯醇（PVA）水凝胶和经过聚（3,4-亚乙基二氧噻吩）（PEDOT）修饰的高电容碳电极制成。hiPSC-CMs 球体在微腔室内培养，并通过电极进行电刺激以成熟。电极的大界面电容即使在电极靠近球体时也能实现数天的电刺激而不会产生细胞毒性气泡。由于水凝胶中渗透的营养物质，球体可以在封闭的微腔室内培养，因此球体可以稳定地寻址，并且可以简单地更换密封微腔室周围的培养基。球体的同步跳动可以在原位进行光学分析，从而可以选择性地收集对电反应的细胞以供进一步使用。由于水凝胶是导电的，因此可以通过在微腔室的顶部和底部配置电极来减少成熟球体所需的电荷量。该生物反应器将有助于高效生产用于再生医学和药物筛选的成熟 hiPSC-CMs。
