Improved osseointegration of dental titanium implants by TiO₂ nanotube arrays with self-assembled recombinant IGF-1 in type 2 diabetes mellitus rat model

Improvement of poor implant osseointegration under diabetes is always a poser in clinics. The purpose of this study was to investigate the effect of TiO2 nanotubes (TNTs) and self-assembled minTBP-1-IGF-1 on implant osseointegration in type 2 diabetes mellitus (T2DM) rats. There were four groups, the control group, the TNTs group, the minTBP-1-IGF-1 group, and the minTBP-1-IGF-1-TNTs group. The atomic force microscopy and scanning electron microscope (SEM) results showed that 500 nm nanotubes were formed by anodic oxidation and minTBP-1-IGF-1 could self-assemble into almost all nanotubes. ELISA assay confirmed that more protein was adsorbed on TNTs surface. The contact angle of the minTBP-1-IGF-1-TNTs group was the lowest, confirmed that the hydrophilicity was the highest. The double fluorescence staining was used to evaluate the mineral apposition rate (MAR) at early stage and the MAR of the minTBP-1-IGF-1-TNTs group was the highest. Micro-CT images displayed that bone formed around the minTBP-1-IGF-1-TNTs implant was the most homogeneous and dense, and the quantitative analysis of these images at 12 weeks also confirmed these results. The cross-section SEM results showed that the connection between bone and minTBP-1-IGF-1-TNTs implant was the tightest. All results demonstrated that minTBP-1-IGF-1-TNTs can significantly improve low implant osseointegration under T2DM condition.