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

• Published in: International journal of nanomedicine Vol. 11; pp. 6307 - 6324
• Main Authors: Liu, Xiangning, Zhang, Ye, Li, Shaobing, Wang, Yayu, Sun, Ting, Li, Zejian, Cai, Lizhao, Wang, Xiaogang, Zhou, Lei, Lai, Renfa
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2016; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Animals; Bioavailability; Bone and Bones - drug effects; Bone Morphogenetic Protein 2 - metabolism; Bone regeneration; Cardiovascular disease; Catalysis; Cytoskeleton - drug effects; Cytoskeleton - metabolism; Dental implants; Drug delivery systems; drug release; Drugs; Female; Hydrodynamics; Hydroxyapatite; Joint surgery; Micelles; Nanoparticles; Nanotubes - chemistry; NMR; Nuclear magnetic resonance; Original Research; orthopedic implant; Osteoblasts - cytology; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteoporosis; Ovariectomy; Polyesters - chemical synthesis; Polyesters - chemistry; Polymers; Prostheses and Implants; Rats, Sprague-Dawley; Studies; targeted drug delivery; Tetracycline - pharmacology; titania nanotubes; Titanium; Titanium - pharmacology; Transplants & implants; X-Ray Microtomography; China; bone regeneration; targeted drug delivery; orthopedic implant; titania nanotubes; drug release; micelles
• DOI: 10.2147/IJN.S119520
• ISSN: 1178-2013; 1176-9114

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.