Bone tissue response following local drug delivery of bisphosphonate through titanium oxide nanotube implants in a rabbit model

Objectives: The objective of this study was to evaluate whether surface chemistry controlled TiO2 nanotube structures may serve as a local drug delivery system for zoledronic acid improving implant-bone support. Methods: Twenty-four screw-shaped Ti implants with surface chemistry-controlled TiO2 nanotube structures were prepared and divided into a zoledronic acid-formatted test and a native control group. The implants were inserted into contra-lateral femoral condyles in 12 New Zealand White rabbits. Bone support was evaluated using resonance frequency analysis (RFA) and removal torque (RTQ), as well as histometric analysis following a 3-weeks healing interval. Results: Zoledronic acid-formatted TiO2 nanotube test implants showed significantly improved implant stability and osseointegration measured using RFA and RTQ compared with control (p<0.05), and showed significantly enhanced new bone formation within the root of the threads compared with control (p<0.05). Conclusions: TiO2 nanotube implants may prove to be a significant delivery system for drugs or biologic agents aimed at supporting local bone formation. Additional study of candidate drugs/agents, optimized dosage and release kinetics is needed prior to evaluation in clinical settings.