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Peer-reviewedCC BY-NC-ND 4.0Advanced Materials (Deerfield Beach, Fla.)

Bottom‐Up Engineering of a Human Neuromuscular System for Modeling Activity‐Induced Remodeling, Metabolic Stress, and Endothelial‐Modulated Excitability

  • Jinchul Ahn1,2
  • Min‐seop Kim3
  • Ju‐Hee Kim3
  • Seok‐Hyeon Kang1
  • Dain Lee3
  • Hui‐Wen Liu1
  • Seung‐cheol Shin3
  • Kyuhwan Na4
  • Yesl Jun5,6
  • Oak‐Kee Hong7
  • Ji Hun Yang8,9
  • Jin‐A Kim3
6 more authors
  • Hwanseok Jang1
  • Hong Nam Kim10,11
  • Roger D. Kamm12,13
  • Ji‐Hoon Kim2
  • Jang‐Won Son14
  • Seok Chung1,3,11
14 affiliations
  1. 1School of Mechanical Engineering Korea University Seoul Republic of Korea
  2. 2Center For Advanced Biomolecular Recognition Korea Institute of Science and Technology (KIST) Seoul Republic of Korea
  3. 3KU‐KIST Graduate School of Converging Science and Technology Korea University Seoul Republic of Korea
  4. 4Samsung Research Samsung Electronics Co., Ltd. Seoul Republic of Korea
  5. 5Therapeutics & Biotechnology Division Korea Research Institute of Chemical Technology Daejeon South Korea
  6. 6Department of Medicinal Chemistry and Pharmacology University of Science and Technology Daejeon Republic of Korea
  7. 7Department of Internal Medicine, College of Medicine The Catholic University of Korea Seoul Republic of Korea
  8. 8Biomedical Research Institute Jeonbuk National University Hospital Jeonju Republic of Korea
  9. 9Research and Development Center Einocle Inc. Seoul Republic of Korea
  10. 10Division of Bio‐Medical Science & Technology KIST School Korea University of Science and Technology (UST) Seoul Republic of Korea
  11. 11Brain Science Institute Korea Institute of Science and Technology (KIST) Seoul Republic of Korea
  12. 12Department of Biological Engineering Massachusetts Institute of Technology Cambridge Massachusetts USA
  13. 13Department of Mechanical Engineering Massachusetts Institute of Technology Cambridge Massachusetts USA
  14. 14Division of Endocrinology and Metabolism Department of Internal Medicine Bucheon St. Mary's Hospital College of Medicine The Catholic University of Korea Seoul Republic of Korea
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{ahn2026bottomup,
  title = {{Bottom‐Up Engineering of a Human Neuromuscular System for Modeling Activity‐Induced Remodeling, Metabolic Stress, and Endothelial‐Modulated Excitability}},
  author = {Jinchul Ahn and Min‐seop Kim and Ju‐Hee Kim and Seok‐Hyeon Kang and Dain Lee and Hui‐Wen Liu and Seung‐cheol Shin and Kyuhwan Na and Yesl Jun and Oak‐Kee Hong and Ji Hun Yang and Jin‐A Kim and Hwanseok Jang and Hong Nam Kim and Roger D. Kamm and Ji‐Hoon Kim and Jang‐Won Son and Seok Chung},
  journal = {Advanced Materials (Deerfield Beach, Fla.)},
  year = {2026},
  month = sep,
  doi = {10.1002/adma.74851},
  url = {https://doi.org/10.1002/adma.74851},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Bottom‐Up Engineering of a Human Neuromuscular System for Modeling Activity‐Induced Remodeling, Metabolic Stress, and Endothelial‐Modulated Excitability
AU  - Jinchul Ahn
AU  - Min‐seop Kim
AU  - Ju‐Hee Kim
AU  - Seok‐Hyeon Kang
AU  - Dain Lee
AU  - Hui‐Wen Liu
AU  - Seung‐cheol Shin
AU  - Kyuhwan Na
AU  - Yesl Jun
AU  - Oak‐Kee Hong
AU  - Ji Hun Yang
AU  - Jin‐A Kim
AU  - Hwanseok Jang
AU  - Hong Nam Kim
AU  - Roger D. Kamm
AU  - Ji‐Hoon Kim
AU  - Jang‐Won Son
AU  - Seok Chung
PY  - 2026
DA  - 2026/09/04
JO  - Advanced Materials (Deerfield Beach, Fla.)
DO  - 10.1002/adma.74851
UR  - https://doi.org/10.1002/adma.74851
AB  - 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.
SN  - 0935-9648
SN  - 1521-4095
ER  -