Surface Immobilization of TiO₂ Nanotubes with Bone Morphogenetic Protein-2 Synergistically Enhances Initial Preosteoblast Adhesion and Osseointegration

Abstract

Although titanium (Ti) alloys have been widely used as implant materials, the bioinertness of pristine Ti impairs their bioactivity and early osseointegration. In the present work, we prepared TiO2 nanotubes (TNT) layer on the titanium (Ti) surface by anodic oxidation. The anodized surface was functionalized with human bone morphogenetic protein-2 coating to form the hBMP-2/TNT surface. The release behavior of hBMP-2 on the hBMP-2/TNT surface displayed a controlled and sustained pattern, compared to that on the hBMP-2/Ti surface, which showed a rapid release. In vitro cellular activity tests demonstrated that both TNT and hBMP-2/Ti surfaces, particularly the hBMP-2/TNT surface, enhanced adhesion, proliferation, and differentiation of osteoblast cells. Increased cell adhesion, improved cytoskeleton organization, and immunofluorescence staining of vinculin were observed on the modified surfaces. The TNT, hBMP-2/Ti, and hBMP-2/TNT surfaces, especially the hBMP-2/TNT surface, further displayed an upregulated gene expression of adhesion and osteogenic markers vinculin, collagen type 1, osteopontin, and osteocalcin, compared to the pristine Ti surface. In vivo experiments using a rat model demonstrated that the TNT and hBMP-2/Ti surfaces, in particular the hBMP-2/TNT surface, improved osseointegration and showed a superior bone bonding ability compared to Ti. Our study revealed a synergistic role played by TiO2 nanotubes nanotopography and hBMP-2 in promoting initial osteoblast adhesion, proliferation, differentiation, and osseointegration, thus suggesting a promising method for better modifying the implant surface.

<p>Zn-Incorporated TiO2 Nanotube Surface Improves Osteogenesis Ability Through Influencing Immunomodulatory Function of Macrophages</p>

“…3,26 Meanwhile, it could also accelerate osseointegration. [27][28][29] The TNT topography was also reported to balance in vitro immune response. 30 However, the mechanism of the immunomodulatory function of the TNT coating has not been fully elucidated.…”

On the Interaction between 1D Materials and Living Cells

“…They followed the expression of integrin β1, osteogenic-related osterix, and alkaline phosphatase, finding that both the MSC adhesion and the osteogenic differentiation improved by increasing the pore size. Interestingly, Li et al [ 86 ] discovered, by using an in vivo rat model, that both bone morphogenetic Protein-2 and TiO 2 NTs enhanced the preosteoblast adhesion and osseointegration in comparison to bare Ti surfaces. The authors justified this behaviour by the sustained release of human bone morphogenetic protein-2 (hBMP-2), in comparison to the hBMP-2/Ti surface, which showed a rapid release.…”

Mechanical Properties of Different Nanopatterned TiO2 Substrates and Their Effect on Hydrothermally Synthesized Bioactive Hydroxyapatite Coatings

“…Nanoscale structures offer surface energy larger than other texture scales, which can improve the adhesion of proteins present in the extracellular matrix (fibronectin, vinculin). The immobilization of biomolecules, such as enzymes or matrix proteins, can be used to stimulate cellular adhesion and migration, which is known as a substantial step in osseointegration processes [ 10 , 11 ]. Functionalizing a surface with other bioactive molecule, such as lectins, can exert different effects on the cellular level, such as the immunomodulatory effect (stimulating the proliferation of lymphocytes and splenocytes) or the inhibition of bacterial and fungal growth [ 12 , 13 ].…”