Sustained Release of Zoledronic Acid from Mesoporous TiO2-Layered Implant Enhances Implant Osseointegration in Osteoporotic Condition

Implant surface modification that provides local sustained release of osteoinductive therapeutic agents enhances implant stability. We designed a mesoporous TiO2-layered titanium implant (MLT) by modified anodization technique that allowed local sustained release of zoledronic acid up to 21 days. Mesoporous layer has pore size 15 nm, depth similar to 30 mu m, volume 0.32 cm(3)/g, surface area 112.3 m(2)/g, surface roughness 20 nm and water contact angle 18.3 degrees. Zoledronic acid-loaded MLT (MLT-Z) was biocompatible, showed anabolic effect on bone forming osteoblasts and catabolic effect on bone resorbing osteoclasts. MLT or MLT-Z implants were implanted in osteoporotic rat-tail vertebrae. Smooth implant in healthy rats were used as a positive control. Histomorphometric analysis showed that bone implant contact of smooth implant in osteoporotic rats was reduced by 4.1-fold compared to healthy rats and MLT-Z rescued the effect by 53%. Similar effect was observed in implant fixation, mechanical stability, BV/TV ratio, Tb.N, Tb.Th and OI% among the groups. Histological and mu-CT images strongly supported the above-mentioned findings. In conclusion, a novel surface-fabricated MLT-Z gives local sustained drug release, robustly enhances implant osseointegration and stability in osteoporotic condition, suggesting it as a promising implant model for patients with compromised bone quality.