Regulation of Osteogenic and Angiogenic Markers in Alkali-Treated Titanium for Hard Tissue Engineering Applications

Titanium (Ti) and Ti alloys are of great interest in bone and dental tissue engineering applications due to their biocompatibility, corrosion resistance, and close mechanical properties to natural bone. However, the formation of fibrous tissue prevents osteointegration and results in implant loosening. Thus, physical and chemical methods are used to improve the surface properties of Ti. This study aimed to understand the role of alkali treatment conditions, including alkali medium concentration, temperature, rotation speed, and post heat treatment. Our results show that alkali treatment using 5 and 10 molar sodium hydroxide (NaOH) solution allows the formation of web-like microstructure. However, a higher concentration of 15 molar resulted in cracks along the surface. Interaction between the human fetal osteoblast cells and Ti samples showed that heat treatment is necessary for increased cellular proliferation, which was not significantly different at later time points compared with the polished Ti. Alkali heat treatment did not induce inflammatory reactions at later time points. It showed an increase in vascular endothelial growth factor, osteoprotegerin/nuclear factor kappa-Β ligand ratio, and osteocalcin expression, which is evidence for accelerated osteoblast cell maturation and bone remodeling in surface-modified samples. Together, these data show that alkali treatment using 5 or 10 molar of NaOH followed by heat treatment may have a therapeutic effect and assist with bone tissue integration with Ti implant.