Immobilizing type I collagen via natural cross-linker genipin to enhance the osteogenic responses to titanium implant surface

Titanium (Ti) surface, with an essentially bioinert character, is not easy to actively initiate interactions with surrounding biological tissue. In this study, we developed a novel surface modification to enhance the osteogenic response to Ti surface in orthopedic and dental implant applications. The proposed surface modification combined alkaline treatment and type I collagen immobilization through using a natural cross-linker genipin. A variety of experiments were used to characterize the resulting surfaces in terms of morphology, chemistry, roughness, hydrophilicity, and bioactivity. We also assessed the responses of human bone marrow mesenchymal stem cells (hMSCs) to Ti surfaces in terms of adhesion, migration, proliferation, mineralization, and differentiation. Results showed that the modified Ti surfaces revealed a hydrophilic (water and diiodomethane contact angles <22°) nano-/submicron-scaled porous network porosity with surface roughness R_a ~0.1 μm and good bioactivity (Ca/P formation ability). The collagen-immobilized Ti surfaces with good coating adhesion was shown to facilitate the mineralization of the extracellular matrix and the expressions of specific osteogenic markers (osteopontin, bone sialoprotein, and osteocalcin) in hMSCs, thanks to improved cell adhesion and migration. Overall, the proposed Ti implant surface modification proved highly effective in terms of promoting osteogenic responses in vitro.