合成生物学 ›› 2024, Vol. 5 ›› Issue (4): 867-882.DOI: 10.12211/2096-8280.2024-065

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骨骼肌芯片及其在生物医学领域的研究进展

王达庆1, 陶婷婷2, 张旭2, 李洪敬1   

  1. 1.大连医科大学附属第一医院,辽宁 大连 116011
    2.中国科学院大连化学物理研究所,辽宁 大连 116023
  • 收稿日期:2024-08-22 修回日期:2024-08-28 出版日期:2024-08-31 发布日期:2024-09-19
  • 通讯作者: 张旭,李洪敬
  • 作者简介:王达庆(1997—),男,骨科学博士研究生。研究方向为关节外科与运动医学。-mail:wangdaqing2020@gmail.com
    张旭(1986—),男,博士,副研究员。研究方向为基于器官芯片的心血管疾病研究。E-mail:zhangxu6@dicp.ac.cn
    李洪敬(1968—),男,医学博士,教授,主任医师,博士生导师。研究方向为关节外科及运动医学。E-mail:lhj68430@163.com
  • 基金资助:
    国家自然科学基金(82102229);大连市“登峰计划”科研项目(DF2023004)

Advances in skeletal muscle-on-a-chip for biomedical research

Daqing WANG1, Tingting TAO2, Xu ZHANG2, Hongjing LI1   

  1. 1.The First Affiliated Hospital of Dalian Medical University,Dalian 116011,Liaoning,China
    2.Dalian Institute of Chemical Physics,Chinese Academy of Sciences,Dalian 116023,Liaoning,China
  • Received:2024-08-22 Revised:2024-08-28 Online:2024-08-31 Published:2024-09-19
  • Contact: Xu ZHANG, Hongjing LI

摘要:

骨骼肌作为人体最丰富的组织之一,是人体运动功能的主要承担者,并且在能量代谢、免疫调节和衰老过程中发挥重要作用。骨骼肌所处的微环境结构复杂,包括多种细胞类型、独特的三维结构以及力学特征。因此,建立高仿生的骨骼肌模型具有一定的挑战性。器官芯片可以精确地模拟人体组织的关键结构和功能特性,从而为骨骼肌模型的建立提供了一种新的途径。本文综述了目前骨骼肌芯片的构建及其在疾病建模、药物评价与再生医学等生物医学研究中的应用。依据人体骨骼肌组织微环境的特点,重点介绍了构建骨骼肌芯片的关键要素,包括动态培养环境、机械刺激、电刺激、血管化与神经化,以及其他工程策略包括各向异性支架的制备与两端锚定的策略等。目前的骨骼肌芯片在细胞来源及功能等方面仍存在一定的局限性。未来通过与基因编辑、生物传感等技术相结合,骨骼肌芯片有望在生物医学研究领域发挥更重要的作用。

关键词: 骨骼肌, 器官芯片, 疾病模型, 药物评价, 再生医学

Abstract:

Skeletal muscle, one of the most abundant tissues in the human body, plays a crucial role in motor function, energy metabolism, immune regulation, and the aging process. The skeletal muscle tissue microenvironment is highly complex, involving a variety of cell types, a three-dimensional architecture, and specific mechanical properties. Replicating these intricate features in vitro to create a biomimetic skeletal muscle model has long posed significant challenges. The advent of organ-on-a-chip technology, which integrates microfluidics with 3D cell culture, offers a groundbreaking approach to faithfully replicate the key structural and functional characteristics of human skeletal muscle tissue. The organ-on-a-chip technology enables precise control over the microenvironment, facilitating the study of skeletal muscle development, disease progression, and drug screening in a highly controlled in vitro setting. The skeletal muscle-on-a-chip (SMoC) has been utilized to investigate a variety of muscle-related diseases, including Duchenne muscular dystrophy and amyotrophic lateral sclerosis, offering valuable insights into disease mechanisms and potential therapeutic strategies. Additionally, SMoC serves as a powerful tool for testing the efficacy and toxicity of new drugs, as well as exploring tissue repair and regeneration techniques. Recent advances in the design and fabrication of SMoCs have further enhanced their physiological relevance, including the incorporation of anisotropic scaffolds to guide muscle fiber alignment and the use of electrical and mechanical stimulation to mimic the native muscle environment. These improvements have led to more accurate disease models and more reliable drug testing platforms, making SMoC a versatile and promising tool in biomedical research. In the end, the prospects and challenges facing the future development of SMoC were discussed. Currently, SMoC still exhibit limitations in terms of cell sources and functionalities. However, the integration with emerging technologies such as gene editing and biosensing in the future could pave the way for significant advancements and breakthroughs. The development of SMoC is expected to further promote the process of translational medicine, with potential applications extending beyond basic research into clinical settings, where it could revolutionize personalized medicine, regenerative therapy and precision drug development.

Key words: skeletal muscle, organs-on-chip, disease modeling, drug testing, regenerative medicine

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