Study of a new bone-targeting titanium implant–bone interface

Abstract

New strategies involving bone-targeting titanium (Ti) implant–bone interface are required to enhance bone regeneration and osseointegration for orthopedic and dental implants, especially in osteoporotic subjects. In this study, a new dual-controlled, local, bone-targeting delivery system was successfully constructed by loading tetracycline-grafted simvastatin (SV)-loaded polymeric micelles in titania nanotube (TNT) arrays, and a bone-targeting Ti implant–bone interface was also successfully constructed by implanting the delivery system in vivo. The biological effects were evaluated both in vitro and in vivo. The results showed that Ti surfaces with TNT–bone-targeting micelles could promote cytoskeletal spreading, early adhesion, alkaline phosphatase activity, and extracellular osteocalcin concentrations of rat osteoblasts, with concomitant enhanced protein expression of bone morphogenetic protein (BMP)-2. A single-wall bone-defect implant model was established in normal and ovariectomized rats as postmenopausal osteoporosis models. Microcomputed tomography imaging and BMP-2 expression in vivo demonstrated that the implant with a TNT-targeting micelle surface was able to promote bone regeneration and osseointegration in both animal models. Therefore, beneficial biological effects were demonstrated both in vitro and in vivo, which indicated that the bone-targeting effects of micelles greatly enhance the bioavailability of SV on the implant–bone interface, and the provision of SV-loaded targeting micelles alone exhibits the potential for extensive application in improving local bone regeneration and osseointegration, especially in osteoporotic subjects.

Keywords:

• bone regeneration
• titania nanotubes
• targeted drug delivery
• orthopedic implant
• drug release
• micelles

Acknowledgments

The authors gratefully acknowledge the assistance by Dr Shan Huang and Dr Xiaoli Gao. This work was supported by Natural Science Foundation of China for young scholars (81300908 and 81400557), National Natural Science Foundation Projects (81370971 and 81170998), the Fundamental Research Funds for the Central Universities (21615480), Guangdong Natural Science Funds for Distinguished Young Scholar (S2013050013880), Natural Science Foundation of Guangdong Province (S2013040014986), Guangdong Science and Technology Foundation (2012B061700091 and 2014A020212634), Medical Scientific Research Foundation of Guangdong Province (C2012034 and 2013B010404032), Guangzhou TianHe Science and Development Project (201504KW020), and Scientific Cultivation Foundation of the First Affiliated Hospital of Jinan University (2015212).

Disclosure

The authors report no conflicts of interest in this work.