Improved osseointegrating functionality of cell sheets on anatase TiO2 nanoparticle surfaces

Abstract

Bone marrow mesenchymal stem cell sheets (BMSC sheets) have been reported as a powerful tool for bioengineering applications in accelerating osseointegration. TiO₂ nanoparticles are beneficial for osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in vitro. Nonetheless, no studies have reported the effects of anatase TiO₂ nanoparticles on the osseointegrating functionality of BMSC sheets in vitro and in vivo. This study is designed to verify the osteogenesis enhancing effects of TiO₂ nanoparticle coated implants on BMSC sheets. In this study, we used a novel light-induced cell sheet method to fabricate BMSC–TiO₂ nanoparticle–implant complexes. The results showed TiO₂ nanoparticles significantly promoted the adhesion and proliferation of cell sheets, and upregulated the expression of osteogenic genes (alkaline phosphatase (ALP), osteocalcin (OCN), Collagen I, bone morphogenetic protein 2 (BMP2), runt-related transcription factor 2 (Runx2) and Osterix) (P < 0.05). In in vivo studies, the results from micro-CT and hard tissue slices showed that the bone-implant contact (BIC) and bone volume per total volume (BV/TV) were significantly higher in the BMSC–TiO₂ nanoparticle–implant group compared with the BMSC–implant group (n = 6, P < 0.05). In conclusion, anatase TiO₂ nanoparticle surfaces could significantly improve the osseointegrating functionality of BMSC sheets. BMSC–TiO₂ nanoparticle–implant complexes are a potential and novel strategy for rapid osseointegration.