Osteogenic Property Of Sr-Dopped TiO₂ Nano-tubes With A Chitosan Coating For Sustained Release Of Icariin

Objectives Osteoporosis is a bone metabolic disease which may negatively affect osseointegration of titanium implants and decrease its success rate.To promote implant osseointegration under osteoporosis,Ti O₂ nano-tubes,loaded with strontium（Sr）and icariin（ICA）,were constructed on titanium surfaces and a chitosan layer was fabricated for controlled slow-release of Sr and icariin.The osteogenic effect of the coating was explored and the results of this study may provide valuable data for clinical application of this new implant loaded with both Sr and icariin.Methods According to different components in coatings,the specimens were divided into five groups:Ti group,Ti O₂ group,Ti O₂+Sr group,Ti O₂+Sr+ICA group,and Ti O₂+Sr+ICA+CS group.Experiments:（1）The surface micro-morphology,element distribution,crystal phase,hydrophilicity and the release of Sr²⁺and ICA from the coatings at different time points were examined by different methods;（2）Cell adhesion,proliferation and osteogenic differentiation In of MC3T3-E1 cells,a preosteoblast line,were also examined in vitro to evaluate the cytocompatibility and osteogenic activity of the coatings;（3）Micro-CT examination was performed to determine the osteogenic property of Sr/icariin-dopped Ti O₂ nano-tubes implants with chitosan coating in vivo.Results（1）Sr/icariin-loaded Ti O₂ nanotubes with a chitosan layer was successfully constructed on the surface of titanium specimens.Incorporation of Sr and icariin did not show significant influence on micromorphology,surface roughness and hydrophilicity of coatings,while chitosan layer decreased the hydrophilicity,increased the roughness of coating,and controlled the release of Sr and icariin.（2）Sr/icariin-loaded Ti O₂ nanotube coating showed both good cytocompatibility and osteogenic property,and promotes preosteoblast adhesion,proliferation and osteogenic differentiation.The chitosan layer on Ti O₂ nanotubes further strengthened the osteogenic effects of Sr and icariin.（3）Sr and icariin within the Ti O₂ nano-tube coating significantly increased the peri-implant bone volume fraction（BV/TV）and implant-bone contact rate（IBCR）in osteoporotic rats,and the chitosan coating further increased BV/TV and IBCR.Conclusions（1）Sr/icariin-loaded Ti O2 nanotubes with a chitosan layer is constructed on titanium surface and the coating manifests good physicochemical properties and controlled release of the drugs,although the physicochemical properties is slightly decreased by the chitosan layer.（2）Incorporation of Sr and icariin can increase osteogenic activity of pre-osteoblasts in vitro and promote their osteogenic differentiation.Chitosan layer furhter increases the osteogenic activity of the coating by controlling slow-release of Sr and icariin.（3）Sr/icariin-loaded Ti O₂ nano-tube coating can promote new bone formation around and osseointegration of titanium implants in osteoporotic rats and chitosan layer further strengthens the osteogenic effect of the coating.Figure 25;Table 6;Reference 149...