Tendon–Bone Healing: Synergistic Role of Platelets and Mesenchymal Stem Cells in Tissue Engineering

Repair of the tendon-bone interface (TBI) remains a significant clinical challenge due to its complex biomechanical environment and hierarchical structure. Conventional surgical approaches often fail to fully reestablish native tissue architecture and function. In recent years, tissue engineering strategies have increasingly emphasized the application of mesenchymal stem cells (MSCs) and platelet-derived products to promote regeneration. MSCs possess multilineage differentiation potential and immunomodulatory capabilities, making them attractive candidates for TBI repair. Platelets, through their rich secretome, orchestrate essential regenerative processes such as cell recruitment, angiogenesis, and immune modulation. This review explores the molecular crosstalk between MSCs and platelets, critically examines current approaches utilizing platelet-rich plasma (PRP)-MSC combinations and platelet-derived exosome therapies and underscores the urgent need for standardization to optimize therapeutic outcomes in PRP-MSC-based regenerative strategies.Impact StatementThis review underscores the critical interplay between platelets and mesenchymal stem cells (MSCs) in tendon-bone healing, highlighting their synergistic roles in promoting osteogenesis, chondrogenesis, angiogenesis, and anti-inflammatory responses. By elucidating the molecular and cellular mechanisms governing these interactions, this work sheds light on potential regenerative therapies that leverage platelet-derived growth factors and MSCs. Such insights aim to optimize healing outcomes for tendon-bone injuries, providing a foundation for innovative clinical strategies that restore the unique and complex structure of the tendon-bone interface.