Skeletal muscle-on-a-chip: an in vitro model to evaluate tissue formation and injury.
Skeletal muscle-on-a-chip: an in vitro model to evaluate tissue formation and injury.
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DOI：
10.1039/c7lc00512a
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发表时间：
2017-10-11
期刊：
影响因子：
6.1
通讯作者：
Varghese S
中科院分区：
文献类型：
--
作者：
Agrawal G;Aung A;Varghese S
工程化骨骼肌组织可用于需要天然组织的生理学相关模型的体外研究。在这里，我们描述了一个三维（3D）骨骼肌组织，概括的微流体装置内的肌肉的建筑和结构的复杂性的发展。使用3D光图案化方法，我们在空间上将载有细胞的明胶网络限制在两个生物惰性水凝胶柱周围，这诱导了细胞的单轴排列，并在包囊细胞和肌肉组织形成和成熟时作为它们的锚定位点。我们已经通过使用荧光显微镜和计算工具的组合表征了细胞分化和骨骼肌组织形成过程中的组织形态和应变分布。时间依赖性应变曲线表明明胶基质内存在单个细胞，其分化形成作为培养时间的函数的多核骨骼肌组织束。我们还开发了一种方法来计算由悬挂在两个支柱之间的工程肌肉组织束产生的被动张力。最后，作为概念验证，我们研究了骨骼肌芯片系统作为筛选平台和体外肌肉损伤模型的适用性。我们研究了心脏毒素对工程化肌肉组织结构的剂量依赖性作用及其随后对被动张力的影响。这种简单而有效的工具可以吸引需要分析骨骼肌结构和功能的研究，包括临床前药物发现和开发。
Engineered skeletal muscle tissues can be used for in vitro studies that require physiologically relevant models of native tissues. Herein, we describe the development of a three-dimensional (3D) skeletal muscle tissue that recapitulates the architectural and structural complexities of muscle within a microfluidic device. Using a 3D photo-patterning approach, we spatially confined a cell-laden gelatin network around two bio-inert hydrogel pillars, which induce uniaxial alignment of the cells and serve as anchoring sites for the encapsulated cells and muscle tissues as they form and mature. We have characterized the tissue morphology and strain profile during differentiation of the cells and skeletal muscle tissue formation by using a combination of fluorescence microscopy and computational tools. The time-dependent strain profile suggests the existence of individual cells within the gelatin matrix, which differentiated to form a multinucleated skeletal muscle tissue bundle as a function of culture time. We have also developed a method to calculate the passive tension generated by the engineered muscle tissue bundles suspended between two pillars. Finally, as a proof-of-concept we have examined the applicability of the skeletal muscle-on-chip system as a screening platform and in vitro muscle injury model. We studied the dose-dependent effect of cardiotoxin on the engineered muscle tissue architecture and its subsequent effect on the passive tension. This simple yet effective tool can be appealing for studies that necessitate the analysis of skeletal muscle structure and function, including preclinical drug discovery and development.
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影响因子：
9.7
作者：
Kang, Heemin;Shih, Yu-Ru V.;Hwang, Yongsung;Wen, Cai;Rao, Vikram;Seo, Timothy;Varghese, Shyni
通讯作者：
Varghese, Shyni
影响因子：
6.1
作者：
Grosberg A;Alford PW;McCain ML;Parker KK
通讯作者：
Parker KK
影响因子：
9.7
作者：
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通讯作者：
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DOI：
10.1073/pnas.1101791108
发表时间：
2011-07-19
影响因子：
11.1
作者：
Chen, Alice A.;Thomas, David K.;Bhatia, Sangeeta N.
通讯作者：
Bhatia, Sangeeta N.
影响因子：
3.9
作者：
Kienhuis, Anne S.;Wortelboer, Heleen M.;Stierum, Rob H.
通讯作者：
Stierum, Rob H.