Hierarchical Peptide Functionalized Titania Nanotubes: Improving Stability, Promoting Osteogenesis, and Reducing Infection Risk.

In this study, a hierarchical surface functionalization strategy was developed that combines engineering of titania nanotubes (TiNTs) on the titanium surface, followed by dual-mode peptide functionalization. Fmoc-FF-OH dipeptide was first covalently anchored onto the TiNT surface, then a secondary layer of the self-assembling FF dipeptide was physically deposited. This technique harnesses the strength of covalent bonds and the extensive surface coverage provided by self-assembling peptides to create a long-lasting, bioactive, and functional surface that promotes superior biocompatibility. The nanotubular topography and peptide-mediated biochemical cues recreate an extracellular matrix-like microenvironment, supporting stem cell adhesion, proliferation, and osteogenic differentiation. Additionally, the self-assembling peptide significantly reduced bacterial adhesion compared to unmodified titanium, demonstrating a marked reduction in bacterial adhesion and early biofilm formation in vitro. Overall, this multifunctional approach combines nanotopographical engineering with peptide-based bioactivity to enhance implant osseointegration and prevent implant-associated infections, offering a promising strategy for next-generation titanium biomedical devices.