Bottom‐Up Engineering of a Human Neuromuscular System for Modeling Activity‐Induced Remodeling, Metabolic Stress, and Endothelial‐Modulated Excitability
In vitro models of the human neuromuscular system recapitulate key features of neuromuscular connectivity and are increasingly used to study disease mechanisms. However, activity-dependent adaptation and the contribution of endothelial cells (ECs) remain incompletely represented in vitro. Here, we establish a bottom-up, microchip-based method that supports motor innervation of three-dimensional (3D) human muscle and permits local or bath application of defined chemical stimuli. The same architecture also supports endothelial ingrowth, producing myobundles with concurrent neural and endothelial integration. Repeated local L-glutamate stimulation induced structural, metabolic, and transcriptional changes associated with activity-dependent muscle adaptation, whereas high-glucose exposure produced a distinct, largely opposing response. Addition of ECs further altered calcium dynamics in motor neurons (MNs) and innervated muscle fibers. This modular method enables controlled investigation of responses to neural, metabolic, and endothelial cues in engineered human neuromuscular system.
Authors
- Seok‐Hyeon Kang
- Kyuhwan Na (ORCID: https://orcid.org/0000-0002-6355-2887)
- Seok Chung (ORCID: https://orcid.org/0000-0002-1735-8338)
- Yesl Jun (ORCID: https://orcid.org/0000-0002-7598-9226)
- Hong Nam Kim (ORCID: https://orcid.org/0000-0002-0329-0029)
- Hwanseok Jang (ORCID: https://orcid.org/0000-0002-1700-5962)
- Hui-Wen Liu
- Seoungyul Shin
- Dain Lee (ORCID: https://orcid.org/0000-0001-6671-5998)
- Jin-Chul Ahn (ORCID: https://orcid.org/0009-0007-7493-4219)
- Jihoon Kim (ORCID: https://orcid.org/0000-0001-7091-8050)
- Ju-Hee Kim (ORCID: https://orcid.org/0000-0001-6380-0425)
- Minseop Kim (ORCID: https://orcid.org/0000-0002-4794-272X)
- Jang Won Son (ORCID: https://orcid.org/0000-0003-0339-0131)
- Ji Hun Yang (ORCID: https://orcid.org/0000-0002-3504-8026)
- Roger D. Kamm (ORCID: https://orcid.org/0000-0002-7232-304X)
- Oak-Kee Hong (ORCID: https://orcid.org/0000-0001-8445-0882)
- Jin‐A Kim (ORCID: https://orcid.org/0009-0003-6768-9332)
Institutions
- Korea Development Institute (KR)
- Korea Institute for Advanced Study (KR)
- Korea Advanced Institute of Science and Technology (KR)
- Korea University (KR)
- Samsung (South Korea) (KR)
- Korea Institute of Brain Science (KR)
- Jeonbuk National University Hospital (KR)
- The Catholic University of Korea Bucheon St. Mary's Hospital (KR)
- Korean Association Of Science and Technology Studies (KR)
- Advanced Analysis Center (JP)
- Korea Research Institute of Chemical Technology (KR)
- Korea Institute of Science and Technology (KR)
- Massachusetts Institute of Technology (US)
- Jeonbuk National University (KR)
- Catholic University of Korea (KR)
- Korea University of Science and Technology (KR)
Publication Details
- Journal
- Advanced Materials
- Published
- 2026-09-04
- DOI
- https://doi.org/10.1002/adma.74851
- Primary Topic
- Advanced Sensor and Energy Harvesting Materials
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Research Foundation
- Ministry of Food and Drug Safety
- Korea Institute of Science and Technology
- National Research Foundation of Korea
- Ministry of Science and ICT, South Korea
- Samsung