Mechanotransduction and its impact on regenerative medicine in orthopedic rehabilitation (Review)

Mechanotransduction, the process by which cells convert mechanical stimuli into biochemical signals, serves as a fundamental biological mechanism driving tissue adaptation and repair in orthopedic rehabilitation. The present review explores how mechanical forces regulate cellular behavior in bone, cartilage, tendon and ligament healing, emphasizing their critical role in optimizing regenerative outcomes. Specialized mechanosensors, including integrins, ion channels and primary cilia, detect physical cues such as compression, tension and shear stress, activating downstream pathways that direct stem cell differentiation, matrix synthesis and tissue remodeling. The extracellular matrix functions not only as a structural scaffold but also as a dynamic mediator of mechanical signaling, influencing cellular responses to therapeutic loading. Clinically, mechanotherapy strategies, including controlled weight‑bearing, eccentric exercises and devices providing dynamic compression, are designed to exploit these principles, promoting anabolic activity while preventing catabolic damage. Advances in biomechanically optimized scaffolds, bioreactor systems and technologies (such as low‑intensity pulsed ultrasound) further demonstrate how targeted mechanical conditioning enhances tissue‑engineered constructs and accelerates functional recovery. However, challenges remain in defining optimal loading parameters across diverse tissues and individual patients. Future directions should prioritize personalized rehabilitation protocols informed by real‑time biomechanical monitoring and genetic profiling, alongside biomaterials that can adapt to in vivo mechanical cues. The integration of mechanobiology with regenerative medicine is paving the way for a new era in orthopedic rehabilitation. This evolution promises more precise, effective and biologically driven interventions that harness the innate mechanoresponsive capacity of the body to restore function.