A clinically translatable coating-free strategy for 3D-printed porous titanium implants: TiO<sub>2</sub> nanotubes simultaneously prevent infection and promote bone integration.

Xiong, Chenao; Zhang, Zhe; Jing, Zehao; Wang, Youhao; Feng, Hui; Yang, Yiyuan; Ni, Renhua; Wei, Chongbin et al. · Bioact Mater · 2026

basic_science · Level V

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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<sub>2</sub> nanotube (TNT) micro/nano hybrid surfaces. The TNT layer features tunable nanoscale dimensions. <i>In vitro</i> 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 <i>Staphylococcus aureus</i> (<i>S. aureus</i>) 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. <i>In vivo</i> 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.