Ornithine−Glycine-Functionalized Titanium Improves Early Peri-Implant Repair under Diabetic Conditions

Abstract Diabetes-associated oxidative stress and microvascular dysfunction compromise the peri-implant healing environment. Here, an ornithine–glycine alternating copolymer (OG) was covalently grafted onto titanium through hydroxylation, KH570 silanization, and polymer immobilization. SEM, AFM, EDS, and XPS confirmed the formation of a roughened, nitrogen-containing organic interface with improved wettability; after 7 and 14 days in simulated body fluid (SBF) or high-glucose SBF (HG-SBF), the characteristic surface texture and nitrogen-associated surface signal remained detectable. Under combined high-glucose and LPS stimulation, Ti-OG improved MC3T3-E1 and HUVEC spreading and metabolic activity. In MC3T3-E1 cells, Ti-OG reduced ROS-associated fluorescence, increased SOD and GPx activities, and increased intracellular NO-associated fluorescence detected by DAF-FM DA. OG functionalization further enhanced osteogenic differentiation and improved HUVEC migration and endothelial network formation, with increased osteogenic-marker expression in MC3T3-E1 cells and higher eNOS and HIF-1α expression in HUVECs. Four weeks after implantation in diabetic rats, Ti-OG showed greater peri-implant bone formation, more favorable trabecular parameters, increased collagen-rich matrix deposition, and higher osteogenic-marker expression. RNA sequencing identified differential expression and enriched pathways associated with cell adhesion, redox regulation, inflammatory responses, and osteogenic processes after OG functionalization. Collectively, these findings indicate that OG functionalization improves cellular responses in vitro and early peri-implant tissue repair in diabetic rats.