Regulation of mesenchymal stem cell osteogenic differentiation through physical interventions: from mechanisms and parameter optimization to clinical translation

Osteogenic differentiation of mesenchymal stem cells (MSCs) serves as the cornerstone of bone tissue engineering and regenerative medicine. Traditional biochemical induction methods exhibit limitations, whereas physical stimulation—as a non-invasive, precise, and controllable regulatory approach—demonstrates significant potential in guiding osteogenic differentiation of MSCs. This review comprehensively examines the biological mechanisms by which diverse physical stimuli (including mechanical forces, matrix properties, electromagnetic fields, low-intensity ultrasound, and photobiomodulation (PBM)) promote osteogenic differentiation in bone marrowderived MSCs (BMSCs), analyzes parameter optimization strategies for multi-modal physical stimulation, and envisions the broad application prospects of intelligent and dynamic biomaterial systems in bone regeneration and tissue repair. Finally, this review proposes key directions for future research, emphasizing the importance of multifactorial synergistic regulation, intelligent precision interventions, development of non-invasive techniques, and clinical translation, aiming to provide theoretical foundations and novel insights for designing next-generation efficient and safe bone regeneration strategies.