EGCG/bimetallic organic framework modified titanium implants: Harmonising anti-inflammatory and antioxidant responses...

Titanium-based repair of diabetic bone defects is often accompanied by oxidative stress, persistent inflammation and poor osseointegration, which need to be urgently addressed. In the present study, p-xylylenebisphosphonate (PXBP) was used to coordinate with Ce ions and Zn^2 + to construct a metal-organic framework structure (Zn/Ce-P-TN) on the surface of titanium dioxide nanorods (TN), and a multifunctional pH-responsive E@Zn/Ce-P-TN coating was obtained by encapsulation with gallic acid (E). The coating had good hydrophilicity, corrosion resistance, and hemocompatibility. E@Zn/Ce-P-TN modulated macrophage polarization toward M2 type by upregulating anti-inflammatory factors (a 2.5-fold increase in CD206 expression) and downregulating pro-inflammatory factors (a 68 % decrease in iNOS expression). In addition, the coating promoted HUVEC migration, lumen formation and expression of angiogenic factors (VEGF upregulation by 3.2-fold). Meanwhile, the coating was able to upregulate the expression of genes and proteins related to osteogenesis and promote osteogenic differentiation of MC3T3-E1 cells. In vivo and in vitro, E@Zn/Ce-P-TN could effectively remove excessive ROS (86.7 % DPPH scavenging) and reduce oxidative stress (80 % ROS reduction in vivo). In vivo, E@Zn/Ce-P-TN also exhibited excellent anti-inflammatory, as well as pro-vascularization and bone regeneration abilities with good biosafety. In conclusion, E@Zn/Ce-P-TN provided an effective strategy for diabetic bone defect repair and was expected to improve clinical outcomes through its multimodal mechanism of action.