A Narrative Review of Titanium Dioxide Nanotubes: Synthesis, Functionalization and Emerging Biomedical Applications

Titanium dioxide (TiO2) nanotubes (TNTs) have emerged as one of the most investigated nanostructured materials in modern surface engineering. Fabricated predominantly by electrochemical anodization of pure or alloyed titanium surfaces, TNTs offer a unique combination of high surface area, adjustable nanotopography, photocatalytic activity, inherent biocompatibility, and hollow tubular architecture capable of accommodating therapeutic agents. These properties render TNTs highly versatile platforms for applications in drug delivery, osseointegration enhancement, antimicrobial surface engineering, and photodynamic therapy. TiO2 nanotubes hold substantial promise for next generation multifunctional implant surface. However, the field is currently constrained by the absence of standardized fabrication protocols, inconsistent reporting of synthesis parameters, a heavy reliance on single cell line in vitro models, and almost completely absent human clinical data. Bridging these gaps requires coordinated efforts in parameter standardization, mechanistic investigation of nanotube-cell interactions at physiologically relevant timescales, and rigorous preclinical in vivo validation before clinical applications can be pursued. This review aims to synthesize the published literature on TiO2 nanotubes from the perspective of biomedical implant science, with particular focus on fabrication parameters, surface functionalization strategies, biological performance outcomes, and the translational gap between laboratory findings and clinical application. Where methodological inconsistencies across studies are identified, probable sources of discrepancy are discussed and directions for standardization are proposed. Overall, TNT geometry emerges as a determining factor of implant performance, but the optimal design for osseointegration does not necessarily coincide with that required for antibacterial activity. This trade off underscores the need for geometry specific optimization, controlled release strategies, and clinically relevant validation before TNT based implant surfaces can be successfully implemented into practice.