Electric‐Field‐Driven Printed 3D Highly Ordered Microstructure with Cell Feature Size Promotes the Maturation of Engineered Cardiac Tissues

• Published in: Advanced science 2023-04, Vol.10 (11), p.e2206264-n/a
• Main Authors: Zhang, Guangming, Li, Wenhai, Yu, Miao, Huang, Hui, Wang, Yaning, Han, Zhifeng, Shi, Kai, Ma, Lingxuan, Yu, Zhihao, Zhu, Xiaoyang, Peng, Zilong, Xu, Yue, Li, Xiaoyun, Hu, Shijun, He, Jiankang, Li, Dichen, Xi, Yongming, Lan, Hongbo, Xu, Lin, Tang, Mingliang, Xiao, Miao
• Format: Article
• Language: English
• Subjects: 3-D printers; 3D highly ordered microstructure; Cardiomyocytes; Cardiovascular disease; Cell Differentiation; cell feature size; Electric fields; electric‐field‐driven; Electrodes; engineered cardiac tissues; Glass substrates; Humans; Induced Pluripotent Stem Cells; Microstructure; Morphology; Myocytes, Cardiac; Printing, Three-Dimensional; small fiber spacing; Tissue engineering; Tissue Engineering - methods
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202206264

Engineered cardiac tissues (ECTs) derived from human induced pluripotent stem cells (hiPSCs) are viable alternatives for cardiac repair, patient‐specific disease modeling, and drug discovery. However, the immature state of ECTs limits their clinical utility. The microenvironment fabricated using 3D scaffolds can affect cell fate, and is crucial for the maturation of ECTs. Herein, the authors demonstrate an electric‐field‐driven (EFD) printed 3D highly ordered microstructure with cell feature size to promote the maturation of ECTs. The simulation and experimental results demonstrate that the EFD jet microscale 3D printing overcomes the jet repulsion without any prior requirements for both conductive and insulating substrates. Furthermore, the 3D highly ordered microstructures with a fiber diameter of 10–20 µm and spacing of 60–80 µm have been fabricated by maintaining a vertical jet, achieving the largest ratio of fiber diameter/spacing of 0.29. The hiPSCs‐derived cardiomyocytes formed ordered ECTs with their sarcomere growth along the fiber and developed synchronous functional ECTs inside the 3D‐printed scaffold with matured calcium handling compared to the 2D coverslip. Therefore, the EFD jet 3D microscale printing process facilitates the fabrication of scaffolds providing a suitable microenvironment to promote the maturation of ECTs, thereby showing great potential for cardiac tissue engineering. A simple, and efficient strategy using electric‐field‐driven jet microscale 3D printing to fabricate 3D highly ordered microstructures with both the fiber width and fiber spacing that match myocardial feature sizes is first developed to build engineered cardiac tissues (ECTs) with hiPSC‐CMs. The myocardial feature‐sized structure promoted the maturation of ECTs, thereby showing great potential for cardiac tissue engineering.