So Hyun Kim1,*,†, Sun-Kyoung Im2,3,*, Soo-Jin Oh2,3,*, Sohyeon Jeong1,4, Eui-Sung Yoon1,4, C. Justin Lee2,5,6, Nakwon Choi1,4 & Eun-Mi Hur2,3,5
1 Center for BioMicrosystems, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea. 2 Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea. 3 Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST), Seoul 02792, Korea. 4 Department of Biomedical Engineering, Korea University of Science and Technology (UST), Daejeon 34113, Korea. 5 Department of Neuroscience, Korea University of Science and Technology (UST), Daejeon 34113, Korea. 6 The KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul 02841, Korea.
* These authors contributed equally to this work.
† Present address: SK Biopharmaceuticals Co., Ltd., Seongnam 13494, Korea.
Correspondence to Nakwon Choi or Eun-Mi Hur.
In native tissues, cellular and acellular components are anisotropically organized and often aligned in specific directions, providing structural and mechanical properties for actuating biological functions. Thus, engineering alignment not only allows for emulation of native tissue structures but might also enable implementation of specific functionalities. However, achieving desired alignment is challenging, especially in three-dimensional constructs. By exploiting the elastomeric property of polydimethylsiloxane and fibrillogenesis kinetics of collagen, here we introduce a simple yet effective method to assemble and align fibrous structures in a multi-modular three-dimensional conglomerate. Applying this method, we have reconstructed the CA3?CA1 hippocampal neural circuit three-dimensionally in a monolithic gel, in which CA3 neurons extend parallel axons to and synapse with CA1 neurons. Furthermore, we show that alignment of the fibrous scaffold facilitates the establishment of functional connectivity. This method can be applied for reconstructing other neural circuits or tissue units where anisotropic organization in a multi-modular structure is desired.