Biological Effects of a Three-Dimensionally Printed Ti6Al4V Scaffold Coated with Piezoelectric BaTiO₃ Nanoparticles on Bone Formation

Abstract

Bone defect repair at load-bearing sites is a challenging clinical problem for orthopedists. Defect reconstruction with implants is the most common treatment; however, it requires the implant to have good mechanical properties and the capacity to promote bone formation. In recent years, the piezoelectric effect, in which electrical activity can be generated due to mechanical deformation, of native bone, which promotes bone formation, has been increasingly valued. Therefore, implants with piezoelectric effects have also attracted great attention from orthopedists. In this study, we developed a bioactive composite scaffold consisting of BaTiO3, a piezoelectric ceramic material, coated on porous Ti6Al4V. This composite scaffold showed not only appropriate mechanical properties, sufficient bone and blood vessel ingrowth space, and a suitable material surface topography but also a reconstructed electromagnetic microenvironment. The osteoconductive and osteoinductive properties of the scaffold were reflected by the proliferation, migration, and osteogenic differentiation of mesenchymal stem cells. The ability of the scaffold to support vascularization was reflected by the proliferation and migration of human umbilical vein endothelial cells and their secretion of VEGF and PDGF-BB. A well-established sheep spinal fusion model was used to evaluate bony fusion in vivo. Sheep underwent implantation with different scaffolds, and X-ray, micro-computed tomography, van Gieson staining, and elemental energy-dispersive spectroscopy were used to analyze bone formation. Isolated cervical angiography and visualization analysis were used to assess angiogenesis at 4 and 8 months after transplantation. The results of cellular and animal studies showed that the piezoelectric effect could significantly reinforce osteogenesis and angiogenesis. Furthermore, we also discuss the molecular mechanism by which the piezoelectric effect promotes osteogenic differentiation and vascularization. In summary, Ti6Al4V scaffold coated with BaTiO3 is a promising composite biomaterial for repairing bone defects, especially at load-bearing sites, that may have great clinical translation potential.

Beta-Titanium Alloy Covered by Ferroelectric Coating–Physicochemical Properties and Human Osteoblast-Like Cell Response

“…For example, when poled surfaces were introduced on ferroelectric potassium sodium niobate ceramics, the number of mouse MC3T3-E1 pre-osteoblasts adhering to these surfaces was higher than on unpoled surfaces [21]. A higher attachment, spreading, and subsequent proliferation was also described in MC3T3-E1 cells on composites of PLGA mixed with poled gadolinium-doped BaTiO3 nanoparticles [28], and in rat bone marrow mesenchymal stem cells on poled BaTiO3 coatings deposited on porous Ti6Al4V scaffolds [18].…”

“…BaTiO3 coating contains positively and negatively charged sites on their surface, which, in addition to their beneficial effect on the adsorption of the cell adhesion-mediating proteins, may facilitate many other cellular processes. These processes include the mitochondrial activity, proteosynthesis, movement of charged molecules inside and outside the cell, and activation of ion channels in the cell membrane, such as Na, K, Cl and particularly Ca channels, which play important role in many vital functions of cells [18,52].…”

“…The positive effect of poling on the growth and osteogenic differentiation of cells can be further enhanced by mechanical loading, which results in manifestations of the piezoelectricity of ferroelectric materials [22]. Piezoelectric effect in BaTiO3 was induced by gravity [26], ultrasound [61], by mechanical loading in a dynamic cell culture system simulating a human motion [24] or by mechanical stimulation after its implantation in vivo into experimental animals [18]. This piezoelectric BaTiO3 showed osteoinductive and osteoconductive effects and an improved osseointegration.…”

“…In addition to the novel types of alloys, a wide range of modifications of the physical and chemical properties of the material surface has been developed in order to enhance its attractiveness for the adhesion and growth of bone cells. These modifications include changes in chemical composition of the material surface (e.g., introduction of various functional groups, which can increase its polarity and wettability), optimization of the surface roughness and morphology [2,3], and particularly creation of electrically active surfaces [15][16][17][18].…”

“…This method can be expected to produce stable BaTiO3 film on TiNb substrates and to coat homogeneously complex shapes of various bone implants. Recently, this method was successfully applied to coat porous 3D-printed Ti6Al4V scaffolds with BaTiO3 in order to improve their interaction with osteogenic cells in vitro and osseointegration in vivo [18].…”