HUVECs’ Expressway Based on Magnesium Ion Doped Hierarchical Scaffold for Rapid Angiogenesis and Bone Ingrowth

Abstract Delayed union or nonunion remains an extremely challenging predicament even after the application of currently available engineering scaffolds for the treatment of critical‐sized bone defects. The angiogenesis throughout the artificial bone repair scaffold to achieve “angiogenic‐osteogenic coupling” is regarded as an effective approach to solving this issue. The newly formed blood vessels can accelerate the supply of oxygen and nutrients, thereby triggering subsequent bone regeneration. Therefore, scaffolds featuring an angiogenic microenvironment that promotes cell adhesion and migration should be designed for superior bone repair. Herein, a magnesium ion‐doped hierarchical scaffold is fabricated using a polymer blend system of chitosan/polyethyleneimine with inherent micro‐phase separation and complexation. Due to the microscopic sea‐island structure and the stable doped magnesium ions, the cell adhesion behavior underwent a significant transformation. Meanwhile, the pathways related to cell adhesion, migration, and angiogenesis are activated, and the critical target thrombospondin 1 is upregulated. Consequently, the cell adhesion capacity is augmented, 6 times the cell migration rate is attained, and the angiogenesis of human umbilical vein endothelial cells is significantly expedited. Eventually, rapid bone ingrowth and satisfactory bone defect repair are approximated in vivo, making the composite scaffold a promising clinical candidate for bone engineering.