Nanometer-thin TiO₂ enhances skeletal muscle cell phenotype and behavior

Ken Ishizaki^*, Yoshihiko Sugita^*, Fuminori Iwasa, Hajime Minamikawa, Takeshi Ueno, Masahiro Yamada, Takeo Suzuki, Takahiro Ogawa
Laboratory for Bone and Implant Sciences, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, UCLA School of Dentistry, Los Angeles, CA, USA
*Authors contributed equally to this work

Background: The independent role of the surface chemistry of titanium in determining its biological properties is yet to be determined. Although titanium implants are often in contact with muscle tissue, the interaction of muscle cells with titanium is largely unknown. This study tested the hypotheses that the surface chemistry of clinically established microroughened titanium surfaces could be controllably varied by coating with a minimally thin layer of TiO₂ (ideally pico-to-nanometer in thickness) without altering the existing topographical and roughness features, and that the change in superficial chemistry of titanium is effective in improving the biological properties of titanium.
Methods and results: Acid-etched microroughened titanium surfaces were coated with TiO₂ using slow-rate sputter deposition of molten TiO₂ nanoparticles. A TiO₂ coating of 300 pm to 6.3 nm increased the surface oxygen on the titanium substrates in a controllable manner, but did not alter the existing microscale architecture and roughness of the substrates. Cells derived from rat skeletal muscles showed increased attachment, spread, adhesion strength, proliferation, gene expression, and collagen production at the initial and early stage of culture on 6.3 nm thick TiO₂-coated microroughened titanium surfaces compared with uncoated titanium surfaces.
Conclusion: Using an exemplary slow-rate sputter deposition technique of molten TiO₂ nanoparticles, this study demonstrated that titanium substrates, even with microscale roughness, can be sufficiently chemically modified to enhance their biological properties without altering the existing microscale morphology. The controllable and exclusive chemical modification technique presented in this study may open a new avenue for surface modifications of titanium-based biomaterials for better cell and tissue affinity and reaction.

Keywords: nanotechnology, orthopedic implants, molten TiO₂ nanoparticles, surface chemistry