Abstract

Objectives Insufficient osseointegration remains a primary cause of early failure in titanium (Ti) dental implants. This study aims to construct a biomimetic hierarchical coating incorporating Ginsenoside Re on Ti substrates via a polydopamine (PDA)-assisted strategy and to systematically evaluate its potential to enhance osteogenic activity. Methods A layer-by-layer assembly approach was employed. A PDA intermediate layer was first formed on Ti via oxidative self-polymerization to improve adhesion and hydrophilicity. Subsequently, hydroxyapatite (HA) was mineralized on the PDA layer, followed by the loading of Ginsenoside Re to fabricate the functionalized surface (TR). Surface characteristics were analyzed using SEM, EDS, XPS, AFM, and water contact angle measurements. The in vitro release behavior of Ginsenoside Re, as well as the biocompatibility, cell adhesion, and osteogenic differentiation of MC3T3-E1 cells, were evaluated using HPLC analysis, CCK-8 assay, CLSM observation, ALP and ARS staining, and qRT-PCR analysis. Results Surface characterization revealed that the TR coating possessed a hierarchical nanotopography composed of nano-sized HA crystallites and exhibited super-hydrophilicity (WCA ∼47.6°). The coating demonstrated excellent biocompatibility, with no cytotoxicity observed. Biologically, the TR surface significantly promoted initial cell spreading and cytoskeletal reorganization, exhibiting the highest nuclear aspect ratio. Furthermore, the TR group displayed superior osteogenic performance, evidenced by a four-fold increase in ALP activity and the significant upregulation of key osteogenic genes (ALP, RUNX2, COL1, OCN, and OPN) compared to the pristine Ti. Conclusions The fabricated TR coating effectively combines physical cues (hierarchical nanotopography and super-hydrophilicity) with chemical signals (sustained release of Ginsenoside Re). This synergistic effect significantly enhances the osteogenic differentiation of MC3T3-E1 cells, suggesti