Titanium-based (Ti-based) nanowire scaffolds are advantageous for promoting cell growth and facilitating tissue regeneration. In addition to the presence of open pores and channels within these scaffolds, it is essential to investigate potential profound underlying mechanisms that contribute to the favorable effects of nanowire scaffolds cell growth. In this study, we found that Ti-based nanowire scaffolds exhibit dynamic tribo-mechanical responsive behavior varying with the number and amplitude of nano-deformation cycles can promote the growth of osteoblasts in culture in vitro. We also found that the scaffolds with strong tribo-mechanical responsive behavior exhibited superior osteoblasts growth compared to the scaffold with weak tribo-mechanical responsive behavior. This work involves the establishment of well-defined interactions between tissues and implants, particularly in relation to tribo-mechanical response conditions.