박시은 (서강대학교)

한빛사논문

조회327

박시은Sieun Park

서강대학교

Chem. Eng. J., Volume 463, 1 May 2023, 142284 | https://doi.org/10.1016/j.cej.2023.142284 Biosensing system for drug evaluation of amyotrophic lateral sclerosis based on muscle bundle and nano-biohybrid hydrogel composed of multiple motor neuron spheroids and carbon nanotubes

Taehyeong Ha ^a,1, Sieun Park ^b,1, Minkyu Shin ^a, Ji-Young Lee ^a, Jin-Ha Choi ^c, Jeong-Woo Choi ^a

^aDepartment of Chemical & Biomolecular Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea
^bDepartment of Biomedical Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea
^cSchool of Chemical Engineering, Jeonbuk National University, 567 Baekje-daero, Deokjin-gu, Jeonju-si, Jeollabuk-do 54896, Republic of Korea

¹These authors equally contributed to this work.
Corresponding authors : Jin-Ha Choi, Jeong-Woo Choi

Abstract

Amyotrophic lateral sclerosis (ALS) results in muscle atrophy due to degeneration of the neuromuscular junctions (NMJs), the synapse responsible for the transmission of signals between motor neurons (MNs) and skeletal muscles. Even though NMJ models have been developed, in vitro drug evaluation models for ALS disease are still lacking due to the absence of a sensing system and immature NMJs in a model system. Moreover, a three-dimensional (3D) biosensing system that can observe drug-induced muscle recovery and movement still does not exist. In this study, we developed the first 3D NMJ biosensing system for drug evaluation of ALS based on muscle bundle and the 3D nano-biohybrid hydrogel composed of multiple motor neuron spheroids (multi-MNSs) and carboxylated carbon nanotubes (CNT-COOH). For the fabrication of biosensor-integrated NMJs, the use of multi-MNSs increased the number of neurites, which in combination with the muscle bundle, resulted in increased NMJ formation. In addition, the use of CNT-COOH in the 3D nano-biohybrid hydrogel induced neurogenesis of multi-MNSs, increased hydrogel conductivity, and formed more mature and functional NMJs. ALS-MNSs obtained from induced pluripotent stem cells (iPSCs) of sporadic ALS patients were added to the 3D nano-biohybrid hydrogel to examine the effects of bosutinib, one of the drug candidates for ALS treatment, leading to the recovery of contraction of the connected muscle bundle. The proposed 3D NMJ biosensing system using 3D nano-biohybrid hydrogel can be an extraordinary platform for drug screening of diverse neuromuscular diseases and toxicity assessment.

논문정보

형식Research article
게재일2023년 05월 (BRIC 등록일 2023-05-02)
연구진국내 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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