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

Abstract

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 ∼30 μm, volume 0.32 cm3/g, surface area 112.3 m2/g, surface roughness 20 nm and water contact angle 18.3°. 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 μ-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.