Nanoporous Titanium Implant Surface Accelerates Osteogenesis via the Piezo1/Acetyl-CoA/β-Catenin Pathway

Osseointegration is the most important factor determining implant success. The surface modification of TiO₂ nanotubes prepared by anodic oxidation has remarkable advantages in promoting bone formation. However, the mechanism behind this phenomenon is still unintelligible. Here we show that the nanomorphology exhibited open and clean nanotube structure and strong hydrophilicity, and the nanomorphology significantly facilitated the adhesion, proliferation, and osteogenesis differentiation of stem cells. Exploring the mechanism, we found that the nanomorphology can enhance mitochondrial oxidative phosphorylation (OxPhos) by activating Piezo1 and increasing intracellular Ca²⁺. The increase in OxPhos can significantly uplift the level of acetyl-CoA in the cytoplasm but not significantly raise the level of acetyl-CoA in the nucleus, which was beneficial for the acetylation and stability of β-catenin and ultimately promoted osteogenesis. This study provides a new interpretation for the regulatory mechanism of stem cell osteogenesis by nanomorphology.