Metal Ion “Adjuvant” [Si─O4] Tetrahedron Addresses Coagulation Interruption and Promotes Multi‐Tissue Regeneration via Smart Ionic Capturing and Cell Membrane Transporting

Abstract Metal ions have regulatory activities of multi‐tissue regeneration but usually interrupt early coagulation, resulting in an abnormal hematoma structure that is not conducive to long‐term repair or regeneration. To address free metal ions immobilization during the coagulation phase and effectively promote ionic bioactivities through controlled macrophage uptake after coagulation, metal ion “adjuvants” are required. [Si─O 4 ] tetrahedron has a unique coordination tetrahedral structure to capture various metal ions and adsorb plasma proteins such as fibrinogen to facilitate macrophage uptake via receptor‐mediated endocytosis during the degradation of the fibrin network. Taking advantage of the hypoxia induction and tissue regeneration ability of copper ions, Cu[Si─O 4 ] tetrahedrons are prepared which successfully immobilized copper ions and addressed the coagulation interruption. Cu[Si─O 4 ] tetrahedrons effectively promote copper ionic uptake by macrophages via LRP1‐mediated endocytosis to create a hypoxia microenvironment and promote periodontal multi‐tissue regeneration. Therefore, [Si─O 4 ] tetrahedron is a kind of advanced multifunctional metal ion “adjuvants” that can capture metal ions and assist their transmembrane transporting to address metal ion‐induced coagulation interruption and promote multi‐tissue regeneration, providing a new strategy for metal ion‐mediated biotherapy research.