Surface functionalization of microgrooved titanium with dual growth factor-releasing nanoparticles for synergistic osteogenic differentiation of human mesenchymal stem cells

We demonstrate that dual release of bone morphogenic protein-2 (BMP-2) and insulin-like growth factor-1 (IGF-1) by catechol-functionalized adhesive polymer nanoparticles on microgrooved titanium (Ti) surface enhances in vitro osteoblastic differentiation of human mesenchymal stem cells (MSCs). The nanoparticles consisted of three distinct domains, surface Ti-adhesive catechol groups, anionic poly(L-aspartic acid) (PAsp) shells, and hydrophobic poly(L-phenylalanine) (PPhe) cores. The immobilization of the adhesive nanoparticles onto microgrooved Ti surface was verified using various surface analytical tools, such as field-emission scanning electron microscopy (Fe-SEM), X-ray photoelectron spectroscopy (XPS), contact angle measurement. The nanoparticles were immobilized both on the groove bottom surface and the ridge top surface with a similar anchoring density. A fluorescence microscope visualized that BMP-2 and IGF-1 of positive charges were efficiently loaded onto the negatively charged PAsp shells of immobilized nanoparticles. We confirmed the enhanced osteoblastic differentiation of MSCs by presenting the expression results of major osteoblast marker genes and proteins. In addition, overall significant correlations between the experimental results verified the validity of our study. The proposed combined surface of microgrooves and growth factor-releasing nanoparticles can be used as a strong osteogenic promoter on various biomaterial surfaces.