한빛사논문
Sohyeon Jeong1,2,3†, Hyun Wook Kang1,4†, So Hyun Kim1,5†, Gyu-Sang Hong1, Min-Ho Nam1, Jihye Seong1,2,6,7, Eui-Sung Yoon1,8, Il-Joo Cho9,10, Seok Chung1,4,11*, Seokyoung Bang1,12*, Hong Nam Kim1,2,13,14*, Nakwon Choi1,11*
1Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea.
2Division of Bio-Medical Science and Technology, KIST School, University of Science and Technology (UST), Seoul 02792, Korea.
3MEPSGEN Co. Ltd., Seoul 05836, Korea.
4School of Mechanical Engineering, Korea University, Seoul 02841, Korea.
5SK Biopharmaceuticals Co. Ltd., Seongnam 13494, Korea.
6Department of Life Sciences, Korea University, Seoul 02841, Korea.
7KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul 02453, Korea.
8Division of Nano and Information Technology, KIST School, University of Science and Technology (UST), Seoul 02792, Korea.
9Department of Biomedical Sciences, College of Medicine, Korea University, Seoul 02841, Korea.
10Department of Anatomy, College of Medicine, Korea University, Seoul 02841, Korea.
11KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Korea.
12Department of Medical Biotechnology, Dongguk University, Goyang 10326, Korea.
13School of Mechanical Engineering, Yonsei University, Seoul 03722, Korea.
14Yonsei-KIST Convergence Research Institute, Yonsei University, Seoul 03722, Korea.
*Corresponding authors: Seok Chung, Seokyoung Bang, Hong Nam Kim, Nakwon Choi
†These authors contributed equally to this work.
Abstract
Anisotropically organized neural networks are indispensable routes for functional connectivity in the brain, which remains largely unknown. While prevailing animal models require additional preparation and stimulation-applying devices and have exhibited limited capabilities regarding localized stimulation, no in vitro platform exists that permits spatiotemporal control of chemo-stimulation in anisotropic three-dimensional (3D) neural networks. We present the integration of microchannels seamlessly into a fibril-aligned 3D scaffold by adapting a single fabrication principle. We investigated the underlying physics of elastic microchannels' ridges and interfacial sol-gel transition of collagen under compression to determine a critical window of geometry and strain. We demonstrated the spatiotemporally resolved neuromodulation in an aligned 3D neural network by local deliveries of KCl and Ca2+ signal inhibitors, such as tetrodotoxin, nifedipine, and mibefradil, and also visualized Ca2+ signal propagation with a speed of ~3.7 μm/s. We anticipate that our technology will pave the way to elucidate functional connectivity and neurological diseases associated with transsynaptic propagation.
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