In vitro modeling of human myotendineous junction for the study of disease and drug testing

The myotendinous junction (MTJ) is a critical interface between skeletal muscle and tendon, responsible for transmitting contractile forces and enabling musculoskeletal movement. Due to its complex architecture, the MTJ is a primary site for injuries, particularly under conditions such as excessive stretching, high-impact activities, aging, and muscular dystrophies. Despite its significance, research on the MTJ is limited due to challenges in accessing human tissue samples, highlighting the need for advanced in vitro models. In this study, we developed a biomimetic 3D MTJ model using patient-derived Pericytes and human tendon-derived stem cells with a core shell 3D wet-spinning technology. This approach enabled the generation of anisotropically aligned fibrous scaffolds that mimic the structural and functional features of the MTJ. Notably, dystrophin expression was observed in both tendon and MTJ-like constructs, suggesting the potential of this model for investigating MTJ degeneration in conditions such as muscular dystrophies. This system offers a more accurate platform for studying musculoskeletal pathologies and developing targeted therapies.