Oriented Neural Spheroid Formation and Differentiation of Neural Stem Cells Guided by Anisotropic Inverse Opals

Lin Xia; Yixuan Shang; Xiangbo Chen; He Li; Xiaochen Xu; Wei Liu; Guang Yang; Tian Wang; Xia Gao; Renjie Chai

doi:10.3389/fbioe.2020.00848

Oriented Neural Spheroid Formation and Differentiation of Neural Stem Cells Guided by Anisotropic Inverse Opals

Front Bioeng Biotechnol. 2020 Jul 31:8:848. doi: 10.3389/fbioe.2020.00848. eCollection 2020.

Authors

Lin Xia¹, Yixuan Shang², Xiangbo Chen^{3

4}, He Li⁵, Xiaochen Xu¹, Wei Liu⁶, Guang Yang⁷, Tian Wang⁶, Xia Gao⁸, Renjie Chai^{1

2

9

10}

Affiliations

¹ MOE Key Laboratory for Developmental Genes and Human Disease, Institute of Life Sciences, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Southeast University, Nanjing, China.
² Department of Clinical Medical Engineering, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
³ Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, China.
⁴ Hangzhou Rongze Biotechnology Group Co., Ltd., Hangzhou, China.
⁵ Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁶ Department of Otolaryngology-Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.
⁷ Department of Otorhinolaryngology, Affiliated Sixth People's Hospital of Shanghai Jiao Tong University, Shanghai, China.
⁸ Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Jiangsu Provincial Key Medical Discipline (Laboratory), Research Institute of Otolaryngology, Nanjing, China.
⁹ Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.
¹⁰ Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.

Abstract

Isotropic inverse opal structures have been extensively studied for the ability to manipulate cell behaviors such as attachment, migration, and spheroid formation. However, their use in regulate the behaviors of neural stem cells has not been fully explored, besides, the isotropic inverse opal structures usually lack the ability to induce the oriented cell growth which is fundamental in neural regeneration based on neural stem cell therapy. In this paper, the anisotropic inverse opal substrates were obtained by mechanically stretching the poly (vinylidene fluoride) (PVDF) inverse opal films. The anisotropic inverse opal substrates possessed good biocompatibility, optical properties and anisotropy, provided well guidance for the formation of neural spheroids, the alignment of neural stem cells, the differentiation of neural stem cells, the oriented growth of derived neurons and the dendritic complexity of the newborn neurons. Thus, we conclude that the anisotropic inverse opal substrates possess great potential in neural regeneration applications.

Keywords: anisotropic inverse opal substrate; neural regeneration; neural stem cells; neurons; oriented growth.