The incorporation of engineered muscle‐tendon junction (MTJ) with organ‐on‐a‐chip technology provides promising in vitro models for the understanding of cell‐cell interaction at the interface between muscle and tendon tissues. However, developing engineered MTJ tissue with biomimetic anatomical interface structure remains challenging, and the precise co‐culture of engineered interface tissue is further regarded as a remarkable obstacle. Herein, an interwoven waving approach is presented to develop engineered MTJ tissue with a biomimetic “M‐type” interface structure, and further integrated into a precise co‐culture microfluidic device for functional MTJ‐on‐a‐chip fabrication. These multiscale MTJ scaffolds based on electrospun nanofiber yarns enabled 3D cellular alignment and differentiation, and the “M‐type” structure led to cellular organization and interaction at the interface zone. Crucially, a compartmentalized co‐culture system is integrated into an MTJ‐on‐a‐chip device for the precise co‐culture of muscle and tendon zones using their medium at the same time. Such an MTJ‐on‐a‐chip device is further served for drug‐associated MTJ toxic or protective efficacy investigations. These results highlight that these interwoven nanofibrous scaffolds with biomimetic “M‐type” interface are beneficial for engineered MTJ tissue development, and MTJ‐on‐a‐chip with precise co‐culture system indicated their promising potential as in vitro musculoskeletal models for drug development and biological mechanism studies.

中文翻译：

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电纺对齐纳米纤维纱线构建的仿生 M 型界面集成到精确的共培养系统中，作为药物开发的芯片上肌肉肌腱连接点

工程化肌肉肌腱连接（MTJ）与芯片上器官技术的结合为理解肌肉和肌腱组织之间界面的细胞间相互作用提供了有前景的体外模型。然而，开发具有仿生解剖界面结构的工程化 MTJ 组织仍然具有挑战性，并且工程化界面组织的精确共培养被进一步认为是一个显着的障碍。在此，提出了一种交织波动方法来开发具有仿生“M型”界面结构的工程MTJ组织，并进一步集成到精确的共培养微流体装置中，用于功能性MTJ片上制造。这些基于电纺纳米纤维纱线的多尺度 MTJ 支架能够实现 3D 细胞排列和分化，并且“M 型”结构导致界面区域的细胞组织和相互作用。至关重要的是，将分区共培养系统集成到 MTJ 芯片设备中，以便同时使用其培养基对肌肉和肌腱区域进行精确共培养。这种 MTJ-on-a-chip 装置进一步用于药物相关的 MTJ 毒性或保护功效研究。这些结果强调，这些具有仿生“M型”界面的交织纳米纤维支架有利于工程化MTJ组织的开发，而具有精确共培养系统的MTJ芯片表明它们作为药物开发的体外肌肉骨骼模型的巨大潜力和生物学机制研究。