RhBMP-2-Loaded PLGA/Titanium Nanotube Delivery System Synergistically Enhances Osseointegration.

Abstract

Although Ti-based implants have been widely used, osseointegration failure can also be found between implants and the surrounding bone tissue, especially in aged patients or in patients with certain systemic diseases. Therefore, in this research, we establish a sustained rhBMP-2 delivery system on a titanium implant surface, an anodic oxidation TiO2 nanotube layer combined with the PLGA film, to enhance osseointegration. This designed system was characterized as follows: surface topography characterization by SEM and AFM; rhBMP-2 release; and the ability to influence MC3T3 cell adhesion, proliferation, and osteogenic differentiation in vitro. Additionally, we evaluated the ability of this system to generate new bone around implants in rabbit tibias by the histological assay and removal torque test. SEM and AFM showed that PLGA membranes were formed on the surfaces of TiO2 nanotube arrays using 1, 3, and 10% PLGA solutions. The 3% PLGA group showed a perfect sustained release of rhBMP-2, lasting for 28 days. Meanwhile, the 3% PLGA group showed improved cell proliferation and osteogenic mRNA expression levels. In the in vivo experiments, the 3% PLGA group had the ability to promote osteogenesis in experimental animals. The anodized TiO2 nanotube coated with a certain thickness of the PLGA layer was an ideal and suitable rhBMP-2 carrier. This modified surface enhances osseointegration and could be useful in clinical dental implant treatment.