Eu-proanthocyanidin/lactoferrin amyloid composite coating: interfacial microenvironment modulation for integrated enhancement of anti-inflammatory, antibacterial, and osteogenic effects.

Titanium implants frequently face challenges such as postoperative infection, inflammation, oxidative stress, and inadequate osseointegration, which limit their clinical restorative efficacy. To overcome these limitations, this study constructed an intermediate TN-PC@Eu layer on TiO2 nanorods via coordination between proanthocyanidins (PC) and Eu3 + , followed by the formation of a composite TN-PC@Eu/LF coating through lactoferrin (LF) phase transition. The resulting coating exhibited pH-responsive release in an infectious microenvironment, enabling the on-demand delivery of PC, Eu3+, and LF. In vitro experiments demonstrated that TN-PC@Eu/LF possessed broad-spectrum antibacterial activity, effectively scavenged ROS to alleviate oxidative stress, and promoted macrophage polarization toward the M2 phenotype while downregulating pro-inflammatory factors. Furthermore, the coating directly enhanced osteogenesis by upregulating osteogenic genes and proteins and improved angiogenesis by promoting endothelial tube formation and vascular-related gene expression. Transcriptomic analysis revealed that osteogenesis was jointly promoted through the modulation of mitochondrial energy metabolism pathways. In rat models of subcutaneous infection and femoral defect, the coating significantly exerted antibacterial, anti-inflammatory, antioxidant, pro-angiogenic, and pro-osteointegrative effects. This study provided a novel strategy for designing functionally integrated coatings with intelligent responsiveness and joint regulatory capacity.