Improved osseointegrating functionality of cell sheets on anatase TiO2 nanoparticle surfaces

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.