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用于药物测试目的的具有衰老表型特征的人类骨骼肌组织的 3D 生物工程模型。

3D-bioengineered model of human skeletal muscle tissue with phenotypic features of aging for drug testing purposes.

机构信息

Institute for Bioengineering of Catalonia (IBEC), The Barcelona Institute of Science and Technology (BIST), Baldiri-Reixac 10-12, 08028 Barcelona, Spain.

Chemistry Department, University of Rome, Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy.

出版信息

Biofabrication. 2021 Aug 16;13(4). doi: 10.1088/1758-5090/ac165b.

DOI:10.1088/1758-5090/ac165b
PMID:34284359
Abstract

Three-dimensional engineering of skeletal muscle is becoming increasingly relevant for tissue engineering, disease modeling and bio-hybrid robotics, where flexible, versatile and multidisciplinary approaches for the evaluation of tissue differentiation, functionality and force measurement are required. This works presents a 3D-printed platform of bioengineered human skeletal muscle which can efficiently model the three-dimensional structure of native tissue, while providing information about force generation and contraction profiles. Proper differentiation and maturation of myocytes is demonstrated by the expression of key myo-proteins using immunocytochemistry and analyzed by confocal microscopy, and the functionality assessed via electrical stimulation and analysis of contraction kinetics. To validate the flexibility of this platform for complex tissue modeling, the bioengineered muscle is treated with tumor necrosis factorto mimic the conditions of aging, which is supported by morphological and functional changes. Moreover, as a proof of concept, the effects of Argireline® Amplified peptide, a cosmetic ingredient that causes muscle relaxation, are evaluated in both healthy and aged tissue models. Therefore, the results demonstrate that this 3D-bioengineered human muscle platform could be used to assess morphological and functional changes in the aging process of muscular tissue with potential applications in biomedicine, cosmetics and bio-hybrid robotics.

摘要

三维工程骨骼肌在组织工程、疾病建模和生物混合机器人领域变得越来越重要,这些领域需要灵活、多功能和多学科的方法来评估组织分化、功能和力测量。本工作展示了一种 3D 打印的生物工程化人类骨骼肌平台,该平台可以有效地模拟天然组织的三维结构,同时提供关于力生成和收缩特性的信息。通过免疫细胞化学检测和共聚焦显微镜分析来证明肌细胞的适当分化和成熟,通过电刺激和收缩动力学分析来评估其功能。为了验证该平台在复杂组织建模中的灵活性,使用肿瘤坏死因子处理生物工程化肌肉以模拟衰老条件,这得到了形态和功能变化的支持。此外,作为概念验证,评估了 Argireline® Amplified peptide(一种导致肌肉放松的化妆品成分)在健康和衰老组织模型中的效果。因此,结果表明,这种 3D 生物工程化人类肌肉平台可用于评估肌肉组织衰老过程中的形态和功能变化,具有在生物医学、化妆品和生物混合机器人领域的潜在应用。

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