Silk fibroin-loaded Fe-curcumin nanoparticles on antimicrobial peptide-functionalized TiO2 nanotube surfaces: Microenvironment-modulated synergy for antibacterial and osteogenic enhancement.

To address the multifaceted clinical challenges of titanium implants in infection, oxidative stress, inflammation, and osseointegration, there is an urgent need to develop multifunctional smart coatings capable of synergistically regulating the local microenvironment. This study constructed a pH-responsive P-TN/SF@Fe-Cur composite coating by loading antibacterial peptide Pt5-1c onto titanium dioxide nanotubes (TN) and utilizing methacrylated silk protein-based hydrogel (SFMA) loaded with iron-curcumin nanoparticles (Fe-Cur NPs) as the sealing layer. Within acidic infectious microenvironments, this coating intelligently released Pt5-1c, Fe3+, and curcumin: Pt5-1c exerted broad-spectrum antibacterial activity by disrupting bacterial cell membranes, resulting in a 77% reduction in viable bacterial counts; Fe3+ might contribute to stabilizing with Pt5-1c to promote endothelial cell migration and expression of angiogenesis markers (CD31, VEGF); while Fe-Cur and Pt5-1c jointly induced M2 polarization of macrophages and effectively scavenged reactive oxygen species, with an 86.75% DPPH radical scavenging rate. Furthermore, this coating exhibited dual functions of direct osteogenesis and immune-regulated osteogenesis, synergistically promoting osteoblastic differentiation with core osteogenic genes (ALP, OCN, COL1a1, RUNX2) upregulated by more than 2.5-fold through multiple pathways including activation of innate immune response regulation, sodium ion transmembrane transporter activity, and glutathione metabolism. In rat subcutaneous infection and femoral defect models, this coating demonstrated significant anti-infective, anti-inflammatory, antioxidant, pro-angiogenic, and pro-osteogenic effects. This study has proposed a novel strategy for fabricating functionally integrated titanium implant coatings with the capacity for synergistic microenvironmental modulation.