多功能生物反应器的开发,以评估循环拉伸和电刺激对肌肉分化的促进作用

IF 6.1 2区 医学 Q1 ENGINEERING, BIOMEDICAL Bioengineering & Translational Medicine Pub Date : 2023-12-07 DOI:10.1002/btm2.10633
Wei-Wen Hu, Yen-Chi Chen, Chia-Wen Tsao, Shen-Liang Chen, Chung-Yuh Tzeng
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摘要

本研究制作多功能生物反应器,探讨电刺激和机械刺激对肌原性分化的促进效果。该生物反应器由在柔性聚二甲基硅氧烷(PDMS)薄膜上沉积聚吡咯(PPy)制备的高度可拉伸导电膜组成。通过调节通道深度,可以调节PPy/PDMS膜的拉伸变形。此外,在6.5 ~ 13%的应变范围内连续循环拉伸24 h, PPy/PDMS的电导率保持不变。该装置可单独或同时进行循环拉伸和电刺激。单次刺激结果显示,循环拉伸或电刺激均可上调肌源性基因表达,促进肌管形成,其中电刺激的改善效果优于循环拉伸。然而,只有循环拉伸才能使C2C12细胞垂直于拉伸方向排列,电刺激不影响细胞形态。肌球蛋白重链(MHC)免疫染色表明,定向细胞在循环拉伸下产生平行肌管。两种刺激组合对肌源性基因调控和肌管形成均有协同作用,且联合电场不影响循环拉伸的定向效应。这些结果表明,这两种处理可能通过不同的途径影响细胞。总的来说,同时应用循环拉伸和电刺激保留了两种刺激的优点,因此可以高度改善肌肉分化以获得丰富的平行肌管,这表明我们开发的多功能生物反应器应该有利于肌肉组织工程的应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Development of a multifunctional bioreactor to evaluate the promotion effects of cyclic stretching and electrical stimulation on muscle differentiation

A multifunctional bioreactor was fabricated in this study to investigate the facilitation efficiency of electrical and mechanical stimulations on myogenic differentiation. This bioreactor consisted of a highly stretchable conductive membrane prepared by depositing polypyrrole (PPy) on a flexible polydimethylsiloxane (PDMS) film. The tensile deformation of the PPy/PDMS membrane can be tuned by adjusting the channel depth. In addition, PPy/PDMS maintained its electrical conductivity under continuous cyclic stretching in the strain range of 6.5%–13% for 24 h. This device can be used to individually or simultaneously perform cyclic stretching and electrical stimulation. The results of single stimulation showed that either cyclic stretching or electrical stimulation upregulated myogenic gene expression and promoted myotube formation, where electrical stimulation improved better than cyclic stretching. However, only cyclic stretching can align C2C12 cells perpendicular to the stretching direction, and electrical stimulation did not affect cell morphology. Myosin heavy chain (MHC) immunostaining demonstrated that oriented cells under cyclic stretching resulted in parallel myotubes. The combination of these two stimuli exhibited synergetic effects on both myogenic gene regulation and myotube formation, and the incorporated electrical field did not affect the orientation effect of the cyclic stretching. These results suggested that these two treatments likely influenced cells through different pathways. Overall, the simultaneous application of cyclic stretching and electrical stimulation preserved both stimuli's advantages, so myo-differentiation can be highly improved to obtain abundant parallel myotubes, suggesting that our developed multifunctional bioreactor should benefit muscle tissue engineering applications.

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来源期刊
Bioengineering & Translational Medicine
Bioengineering & Translational Medicine Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
8.40
自引率
4.10%
发文量
150
审稿时长
12 weeks
期刊介绍: Bioengineering & Translational Medicine, an official, peer-reviewed online open-access journal of the American Institute of Chemical Engineers (AIChE) and the Society for Biological Engineering (SBE), focuses on how chemical and biological engineering approaches drive innovative technologies and solutions that impact clinical practice and commercial healthcare products.
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