A clinically translatable coating-free strategy for 3D-printed porous titanium implants: TiO2 nanotubes simultaneously prevent infection and promote bone integration

Abstract

Orthopedic implants face persistent clinical challenges of peri-implant infection and impaired osseointegration, especially in high-risk populations with trauma, osteoporosis, or diabetes. Herein, we report a coating-free strategy integrating three-dimensional (3D) printing and electrochemical anodization to fabricate porous titanium alloy implants with TiO 2 nanotube (TNT) micro/nano hybrid surfaces. The TNT layer features tunable nanoscale dimensions. In vitro evaluations demonstrate that TNT surfaces exert diameter-dependent biological effects: small-diameter TNTs favor early human bone marrow mesenchymal stem cell (hBMSC) adhesion and proliferation, whereas large-diameter TNTs exhibit the strong antibacterial activity and potent osteogenic differentiation potential. Additionally, TNTs induce transient early M1 macrophage polarization, which synergizes with intrinsic contact-mediated antibacterial activity to accelerate pathogen clearance. Mechanistic investigations reveal that TNTs inhibit Staphylococcus aureus ( S. aureus ) adhesion and biofilm formation by downregulating topoisomerase I (TopA) to disrupt bacterial DNA topology homeostasis. For osteogenesis, TNTs modulate Filamentous actin (F-actin) cytoskeleton organization and XB130 adaptor protein expression in hBMSCs, thereby activating the PI3K/Akt/GSK3β/β-catenin signaling pathway to drive osteogenic differentiation. In vivo studies using rabbit femoral condyle models confirm that TNT implants exhibit markedly reduced bacterial burden in an infection model and enhanced bone-implant integration. Collectively, these results indicate that TNT 3D-printed titanium implants offer a synergistic platform combining antibacterial defense and enhanced osteointegration. This work provides a mechanistic understanding and preclinical validation for a clinically translatable surface-engineering strategy for next-generation orthopedic implants.