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─O₄] 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─O₄] tetrahedrons are prepared which successfully immobilized copper ions and addressed the coagulation interruption. Cu[Si─O₄] 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─O₄] 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.