Enhancing the biological response of titanium surface through the immobilization of bone morphogenetic protein-2 using the natural cross-linker genipin

• BMP-2 was successfully immobilized on Ti surfaces using natural cross-linker genipin.
• BMP-2 immobilized Ti surfaces provide good hydrophilicity and protein adsorption.
• BMP-2 immobilized Ti surfaces present good coating adhesion and non-cytotoxicity.
• BMP-2 immobilized Ti surfaces promote cell mineralization and bioactivity.
• Proposed process is simple, cost-effective, and suited to bone implant applications.

Titanium (Ti) is widely used in orthopaedic and dental implants; however, the surface modification methods used to promote osseointegration require further development. In this study, we developed a simple, cost-effective method for the immobilization of bone morphogenetic protein-2 (BMP-2) on Ti surfaces using a natural cross-linker genipin. We then investigated the surface characteristics, including topography, chemistry, hydrophilicity, coating layer adhesion, and protein (albumin) adsorption. In accordance with ISO 10993-5, the cytotoxicity of the resulting materials was evaluated. Human bone marrow mesenchymal stem cell responses, including adhesion, proliferation, and mineralization, were also evaluated. Immersion in alkaline solution resulted in the formation of a porous Ti surface. The use of the cross-linker genipin for the immobilization of BMP-2 on porous Ti surfaces improved the surface hydrophilicity and protein adsorption, which resulted in a non-cytotoxic coating with good adhesion characteristics. The immobilization of BMP-2 on porous Ti surfaces was shown to significantly increase cell mineralization and bioactivity (i.e. Ca/P formation ability), resulting in a biomolecular surface with outstanding potential for bone implant applications.