Electrospun Aligned Nanofiber Yarns Constructed Biomimetic M‐Type Interface Integrated into Precise Co‐Culture System as Muscle‐Tendon Junction‐on‐a‐Chip for Drug Development

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. This study presents an interwoven waving approach to develop engineered muscle‐tendon junction (MTJ) tissue with an “M‐type” interface structure based on electrospun nanofiber yarns, and further integrated into a precise co‐culture microfluidic device for biomimetic MTJ‐on‐a‐chip fabrication. The drug‐associated MTJ toxic or protective efficacy investigations on MTJ‐on‐a‐chip suggest its promising potential as in vitro musculoskeletal models for drug development.