Controlled release of bone morphogenetic protein (BMP)-2 from nanocomplex incorporated on hydroxyapatite-formed titanium surface

• DOI: 10.1016/j.jconrel.2012.04.021
• Publication Date: 2012-04-21T19:56:07Z
• Authors: Soon Eon Bae; Jiyeon Choi; Yoon Ki Joung; Kwideok Park; Dong Keun Han
• Keywords: Titanium; Osteoblasts; Osteocalcin; Bone Morphogenetic Protein 2; Gene Expression; 02 engineering and technology; Hydrogen-Ion Concentration; Alkaline Phosphatase; Collagen Type I; Recombinant Proteins; Cell Line; Mice; Durapatite; Delayed-Action Preparations; Animals; Nanoparticles; Calcium; Particle Size; 0210 nano-technology; Cell Proliferation

Both osteoconductivity and osteoinductivity are equally very important aspects in a new bone formation and ultimately for bone regeneration. The purpose of this study was to create an environment, not only osteoconductive but also osteoinductive on titanium (Ti) surface. To do this bone morphogenetic protein-2 (BMP-2) nanocomplex (NC) was fabricated by using an ionic interaction between BMP-2 and chondroitin sulfate (CS). Meanwhile, Ti was chemically treated, then subjected to soaking in simulated body fluid (SBF), naming the sample Ti(C)-hydroxyapatite (HA). Once the BMP-2 NC was precipitated on the Ti(C)-HA surface, along with the addition of calcium/phosphate solution, the final product was formed as Ti(C)-HA-BMP-2. The size of NC was ranged from 150 to 250nm and the amount of CS was influential in determining both NC size and zeta potential. From the SEM observation, Ti surface was found nicely covered with the crystallized apatite layer that was identified using FTIR and NMR. The immobilized BMP-2 was released in a moderate rate for 4 weeks, without an initial burst of BMP-2. When mouse osteoblast cells were seeded on different Ti substrates, cell proliferation was faster in the Ti(C)-HA-BMP-2 group, as compared to other groups. The gene expression of bone-specific markers, osteocalcin and type I collagen, was significantly upregulated with the use of BMP-2 NC. The same result was witnessed in the measurement of alkaline phosphatase activity, in which the difference was statistically significant. This study demonstrated that the delivery system of BMP-2 NC was effective in holding BMP-2 on the apatite-coated Ti surface and that the Ti surface could be modified into the environment osteoinductive as well as osteoconductive.