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.