Varieties of pathological conditions, including diabetes, are closely related to oxidative stress (OS), but the osseointegration or bioadaptation of implants to OS and the related mechanism remain poorly explored. In this study, the antioxidation and osteoimmune regeneration of titanium implants with micro/nanotopographies were evaluated under H 2 O 2 -, lipopolysaccharide (LPS)- and hyperglycemia-mediated cellular OS models and in diabetic rats as a representative animal model of OS. TiO 2 nanotube (TNT) coating on titanium implants directly induced superior osteogenic differentiation of bone mesenchymal stem cells (MSCs) and osseointegration compared with microscale sand blasted-acid etched topography (SLA) under OS, attributed to higher superoxide dismutase 2 activity, the neutralization of intracellular reactive oxygen species (ROS), and less apoptosis. Mechanistically, the oxidation resistance on TNT is driven by upregulated forkhead box transcription factor O1 (FoxO1), which is abolished after knockdown of FoxO1 via shRNA in MSCs. Indirectly, TNT also alleviates OS in macrophages, therefore inducing a higher portion of the M2 phenotype under OS with increased secretion of the anti-inflammatory cytokine IL-10, further promoting the osseoimmunity capacity compared with SLA. The current study not only suggests the potential application of TiO 2 nanotube-coated titanium implants in compromised conditions but also provides a systematic evaluation strategy for the future development of bone biomaterials.

Current evidence has suggested that diabetes increases the risk of implanting failure, and therefore, appropriate surface modification of dental implants in patients with diabetes is crucial. TiO2 nanotube (TNT) has an osteogenic nanotopography, and its osteogenic properties can be further improved by loading appropriate drugs. Cinnamaldehyde (CIN) has been proven to have osteogenic, anti-inflammatory, and anti-bacterial effects. We fabricated a pH-responsive cinnamaldehyde-TiO2 nanotube coating (TNT-CIN) and hypothesized that this coating will exert osteogenic, anti-inflammatory, and anti-bacterial functions in a simulated diabetes condition. TNT-CIN was constructed by anodic oxidation, hydroxylation, silylation, and Schiff base reaction to bind CIN, and its surface characteristics were determined. Conditions of diabetes and diabetes with a concurrent infection were simulated using 22-mM glucose without and with 1-μg/mL lipopolysaccharide, respectively. The viability and osteogenic differentiation of bone marrow mesenchymal stem cells, polarization and secretion of macrophages, and resistance to Porphyromonas gingivalis and Streptococcus mutans were evaluated. CIN was bound to the TNT surface successfully and released better in low pH condition. TNT-CIN showed better osteogenic and anti-inflammatory effects and superior bacterial resistance than TNT in a simulated diabetes condition. These findings indicated that TNT-CIN is a promising, multifunctional surface coating for patients with diabetes needing dental implants.