Speaker
Description
The myotendinous junction (MTJ) is a highly specialized interface that connects skeletal muscle to tendon, enabling the transmission of contractile forces and ensuring efficient biomechanical performance of the musculoskeletal system. Functionally, the MTJ plays a pivotal role in maintaining structural continuity between two developmentally distinct tissues—muscle and tendon—while withstanding dynamic mechanical stresses during movement. Due to its complex, interdigitated architecture and constant exposure to high loads, the MTJ is particularly prone to damage under conditions of excessive stretching, repetitive mechanical strain, aging, and neuromuscular pathologies such as muscular dystrophies. In such conditions, microstructural discontinuities at the MTJ can result in compromised force transmission, tissue degeneration, and impaired motor function. Despite its critical physiological relevance, research focused on the MTJ remains limited, primarily due to the scarcity of human tissue samples and the lack of representative in vitro models that can recapitulate its architectural and cellular complexity.
To address this gap, we present the development of a fully human, biomimetic 3D MTJ-like model using rotary wet-spinning (RoWS) technology. This platform allows the precise spatial deposition of different human cell populations into aligned core–shell fiber architectures, enabling the creation of compartmentalized tissue constructs that mimic the anisotropic organization of the native junction. In this study, human primary pericytes (hPeri), representing a muscle-related lineage, and human tendon-derived stem cells (hTDSCs), involved in tendon regeneration, were sequentially loaded and extruded using the RoWS system to form structured, multicellular scaffolds. The resulting constructs demonstrated high structural integrity, anisotropy, and mechanical cohesion between muscle and tendon regions, faithfully replicating key aspects of MTJ organization.
Immunofluorescence analysis confirmed the spatially localized expression of lineage-specific markers. hTDSCs expressed tenogenic markers such as collagen I, collagen III, tenascin-C, and tenomodulin, while hPeri differentiated into myogenic domains positive for myosin heavy chain (MHC), indicative of functional muscle maturation. Notably, cells at the interface region exhibited organized interdigitations between the two compartments, resembling the transition zone of native MTJ tissue. Most significantly, expression of dystrophin—a protein classically associated with muscle fiber stability—was detected not only in the muscle region but also at the MTJ-like interface and within the tendon compartment. This unexpected localization suggests a potential, underexplored role for dystrophin in maintaining MTJ integrity and opens new avenues for studying its involvement in the progression of muscle-tendon degeneration in dystrophic conditions.
The modular and human-based nature of this platform offers several advantages over traditional co-culture or animal-derived models. The use of primary human cells enhances physiological relevance and translational potential, while the compartmentalized RoWS fabrication process ensures reproducibility and spatial control. Furthermore, the construct’s compatibility with standard analytical techniques makes it well-suited for downstream applications such as disease modeling, mechanical stimulation studies, and pharmacological screening.
In conclusion, our engineered 3D MTJ-like model provides a robust, reproducible, and scalable platform for investigating human musculoskeletal physiology, injury mechanisms, and therapeutic interventions. This work represents a significant step toward the establishment of clinically relevant in vitro tools to study MTJ pathology and regeneration.
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