Advances in Construction Strategies and Applications of Locomotor System Organoids Based on Bioactive Materials

Abstract The locomotor system organoids, which recapitulate bones, cartilage, tendons, muscles, and associated neurovascular-like structures, possess complex architecture and biomechanical properties. Traditional two-dimensional (2D) cell models struggle to effectively mimic their physiological functions. Organoid technology, through three-dimensional (3D) culture and cellular self-organization, offers an innovative paradigm for modeling developmental and pathological processes of the locomotor system. However, accurately constructing locomotor system organoids with highly biomimetic properties still presents the core challenge of reconstructing the extracellular matrix (ECM), the mechanical microenvironment, and dynamic biological cues. Bioactive materials, such as natural hydrogels, decellularized matrices (dECM), and synthetic hydrogels, serve as key supporting materials, not only providing a 3D scaffold for cells but also guiding stem cell differentiation and tissue self-organization by modulating physicochemical properties and biological cues. From the perspective of material-driven microenvironment regulation, this paper systematically reviews the construction strategies, research progress and translational applications of locomotor system organoids, analyzes the key challenges of standardization, vascularization and immune microenvironment integration. Finally, the integrated application of intelligent responsive materials, four-dimensional bioprinting and artificial intelligence is prospected to provide a future direction for the biomimetic optimization and clinical translation of locomotor system organoids.