Advances Focusing on the Application of Various Ions in Tendon–Bone Healing

The tendon-bone interface (TBI) possesses a highly intricate structure, making complete restoration of its native structure postinjury particularly challenging, which often leads to suboptimal healing outcomes. Metal ions, such as calcium (Ca²⁺), magnesium (Mg²⁺), zinc (Zn²⁺), copper (Cu²⁺), cobalt (Co²⁺), strontium (Sr²⁺), iron (Fe^2+/Fe³⁺), and lithium (Li⁺), have attached significant attention in tissue regeneration research owing to the excellent roles in promoting angiogenesis, osteogenesis, and chondrogenesis. This review systematically elucidates a comprehensive overview of the current understanding of these bioactive ions' mechanisms and their applications in TBI repair. Additionally, the review highlights the importance of incorporating metal ions into biomaterial scaffolds to enhance simultaneous multitissue regeneration while addressing current therapeutic limitations in TBI management. Finally, the review outlines future research directions for optimizing ion-based biomaterial strategies to advance TBI treatment paradigms. Impact Statement The tendon-bone interface (TBI) repair is challenging due to the structural complexity. While a lot of research has focused on restoring TBI functionally and structurally, there is no good strategy to achieve its complete repair. Metal ions play certain roles in promoting the repair of TBI. Therefore, this paper discussed the role of metal ions and materials applied to the TBI in the repair process and related mechanisms, aiming to provide reference for subsequent studies.