Promoting Long-Term Cultivation of Motor Neurons for 3D Neuromuscular Junction Formation of 3D In Vitro Using Central-Nervous-Tissue-Derived Bioink,Advanced Healthcare Materials

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Promoting Long-Term Cultivation of Motor Neurons for 3D Neuromuscular Junction Formation of 3D In Vitro Using Central-Nervous-Tissue-Derived Bioink
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2021-08-07 , DOI: 10.1002/adhm.202100581
Jeong Sik Kong ₁ , Xuan Huang ₂ , Yeong-Jin Choi _{3,

4} , Hee-Gyeong Yi _{3,

5} , Junsu Kang ₃ , Sejin Kim ₃ , Jongmin Kim ₃ , Hyungseok Lee _{3,

6,

7} , Yeri Alice Rim ₈ , Ji Hyeon Ju ₈ , Wan Kyun Chung ₃ , Clifford J Woolf ₂ , Jinah Jang _{1,

3,

9,

10} , Dong-Woo Cho _{1,

3,

10}

Affiliation

School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk, 37673, Republic of Korea.
FM Kirby Neurobiology Center, Boston Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA, 02115, USA.
Department of Mechanical Engineering, Pohang University of Science and Technology, (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk, 37673, Republic of Korea.
Materials Processing Innovation Research Division, Korea Institute of Materials Science (KIMS), 797 10 Changwondaero, Kyungnam, Changwon, 51508, Republic of Korea.
Department of Rural and Biosystems Engineering, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, 61186, Republic of Korea.
Department of Mechanical and Biomedical Engineering, Kangwon National University (KNU), 1 Gangwondaehak-gil, Seoksa-dong, Chuncheon-si, Gangwon-do, 24341, Republic of Korea.
Interdisciplinary Program in Biohealth-Machinery Convergence Engineering, Kangwon National University (KNU), Chuncheon, 24341, Republic of Korea.
Catholic iPSC Research Center, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Republic of Korea.
Department of Convergence IT Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-ro, Nam-gu, Pohang, Kyungbuk, 37673, Republic of Korea.
Institute for Convergence Research and Education in Advanced Technology, Yonsei University, Seoul, 03722, Republic of Korea.

3D cell printing technology is in the spotlight for producing 3D tissue or organ constructs useful for various medical applications. In printing of neuromuscular tissue, a bioink satisfying all the requirements is a challenging issue. Gel integrity and motor neuron activity are two major characters because a harmonious combination of extracellular materials essential to motor neuron activity consists of disadvantages in mechanical properties. Here, a method for fabrication of 3D neuromuscular tissue is presented using a porcine central nervous system tissue decellularized extracellular matrix (CNSdECM) bioink. CNSdECM retains CNS tissue-specific extracellular molecules, provides rheological properties crucial for extrusion-based 3D cell printing, and reveals positive effects on the growth and maturity of axons of motor neurons compared with Matrigel. It also allows long-term cultivation of human-induced-pluripotent-stem-cell-derived lower motor neurons and sufficiently supports their cellular behavior to carry motor signals to muscle fibers. CNSdECM bioink holds great promise for producing a tissue-engineered motor system using 3D cell printing.

中文翻译：

使用中枢神经组织衍生的 Bioink 促进运动神经元的长期培养，用于 3D 体外 3D 神经肌肉连接形成

3D 细胞打印技术是生产可用于各种医学应用的 3D 组织或器官构造的焦点。在神经肌肉组织的打印中，满足所有要求的生物墨水是一个具有挑战性的问题。凝胶完整性和运动神经元活动是两个主要特征，因为对运动神经元活动必不可少的细胞外材料的和谐组合包括机械性能的缺点。在这里，提出了一种使用猪中枢神经系统组织脱细胞细胞外基质 (CNSdECM) 生物墨水制造 3D 神经肌肉组织的方法。CNSdECM 保留 CNS 组织特异性细胞外分子，提供对基于挤出的 3D 细胞打印至关重要的流变特性，并揭示了与 Matrigel 相比对运动神经元轴突生长和成熟的积极影响。它还允许长期培养人类诱导的多能干细胞衍生的下运动神经元，并充分支持它们的细胞行为，将运动信号传送到肌肉纤维。CNSdECM bioink 有望利用 3D 细胞打印生产组织工程电机系统。

更新日期：2021-09-22

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