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

Abstract

Xiangning Liu,1,* Ye Zhang,1,* Shaobing Li,2,* Yayu Wang,3 Ting Sun,1 Zejian Li,1 Lizhao Cai,1 Xiaogang Wang,3,* Lei Zhou,2 Renfa Lai1 1The Medical Center of Stomatology, The First Affiliated Hospital of Jinan University, 2The Department of Oral Implantology, Guangdong Provincial Stomatological Hospital, Southern Medical University, 3Department of Cell Biology, Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou, People’s Republic of China *These authors contributed equally to this work 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

Keywords

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