Mechanical properties and biocompatibility of a novel miniscrew made of Zr70Ni16Cu6Al8 bulk metallic glass for orthodontic anchorage.

The purpose of the present study was to fabricate a miniscrew possible for clinical application using Zr70Ni16Cu6Al8 bulk metallic glass (BMG), which has high mechanical strength, low elastic modulus, and high biocompatibility. First, the elastic moduli of Zr-based metallic glass rods made of Zr55Ni5Cu30Al10, Zr60Ni10Cu20Al10, Zr65Ni10Cu17.5Al7.5, Zr68Ni12Cu12Al8, and Zr70Ni16Cu6Al8 were measured. Zr70Ni16Cu6Al8 had the lowest elastic modulus among them. Then, we fabricated Zr70Ni16Cu6Al8 BMG miniscrews with diameters from 0.9 to 1.3 mm, conducted a torsion test, and implanted them into the alveolar bone of beagle dogs to compare insertion torque, removal torque, Periotest, new bone formation around the miniscrew, and failure rate compared with 1.3 mm diameter Ti-6Al-4 V miniscrew. The Zr70Ni16Cu6Al8 BMG miniscrew exhibited a high torsion torque even if the miniscrew had a small diameter. Zr70Ni16Cu6Al8 BMG miniscrews with a diameter of 1.1 mm or less had higher stability and lower failure rate than 1.3 mm diameter Ti-6Al-4 V miniscrews. Furthermore, the smaller diameter Zr70Ni16Cu6Al8 BMG miniscrew was shown, for the first time, to have a higher success rate and to form more new bone around the miniscrew. These findings suggested the usefulness of our novel small miniscrew made of Zr70Ni16Cu6Al8 BMG for orthodontic anchorage.

Biosafety, stability, and osteogenic activity of novel implants made of Zr70Ni16Cu6Al8 bulk metallic glass for biomedical application.

Superior mechanical and chemical properties of Zr70Ni16Cu6Al8 bulk metallic glass (BMG) demonstrate its promise as a novel biomaterial for fabrication of implants. The aim of the present study was to validate mechanical, chemical, and biological properties of Zr70Ni16Cu6Al8 BMG through comparison with titanium (Ti). Our data indicated higher tensile strength, lower Young's modulus, and reduced metal ion release of Zr70Ni16Cu6Al8 BMG compared with Ti. Biosafety of bone marrow mesenchymal cells on Zr70Ni16Cu6Al8 BMG was comparable to that of Ti. Next, screw-type implant prototypes made of Zr70Ni16Cu6Al8 BMG were fabricated and inserted into rat long bones. Zr70Ni16Cu6Al8 BMG implants indicated a higher removal-torque value and lower Periotest value compared with Ti implants. In addition, higher amounts of new bone formation and osseointegration were observed around Zr70Ni16Cu6Al8 BMG implants compared with Ti implants. Moreover, gene expression analysis displayed higher expression of osteoblast- and osteoclast-associated genes in the Zr70Ni16Cu6Al8 BMG group compared with the Ti group. Importantly, loading to implants upregulated bone formation, as well as osteoblast- and osteoclast-associated gene expression in the peri-implant area. No significant difference in concentrations of Ni, Al, Cu, and Zr in various organs was shown between in the Zr70Ni16Cu6Al8 BMG and Ti groups. Collectively, these findings suggest that Zr70Ni16Cu6Al8 BMG is suitable for fabricating novel implants with superior mechanical properties, biocompatibility, stability, and biosafety compared with Ti. STATEMENT OF SIGNIFICANCE: Titanium is widely used to fabricate orthopedic and dental implants. However, Titanium has disadvantages for biomedical applications in regard to strength, elasticity, and biosafety. Recently, we developed a novel hypoeutectic Zr70Ni16Cu6Al8 BMG, which has superior mechanical and chemical properties. However, the validity of Zr70Ni16Cu6Al8 BMG for biomedical application has not been cleared. The aim of the present study was to validate the mechanical, chemical, and biological properties of Zr70Ni16Cu6Al8 BMG for biomedical applications through comparison with Titanium. The present study clarifies that Zr70Ni16Cu6Al8 BMG has good mechanical properties, corrosion resistance, and osteogenic activity, which are necessary features for biomedical applications. The present study provides for the first time the superiority of Zr70Ni16Cu6Al8 BMG implants to Titanium implants for biomedical applications.

In vivo expression and regulation of genes associated with vascularization during early response of sutures to tensile force.

Sutures are fibrous tissues that connect bones in craniofacial skeletal complexes. Cranio- and dentofacial skeletal deformities in infant and adolescent patients can be treated by applying tensile force to sutures to induce sutural bone formation. The early gene expression induced by mechanical stress is essential for bone formation in long bones; however, early gene expression during sutural bone formation induced by tensile force is poorly characterized. In vivo studies are essential to evaluate molecular responses to mechanical stresses in heterogeneous cell populations, such as sutures. In this paper we examined in vivo early gene expression and the underlying regulatory mechanism for this expression in tensile-force-applied cranial sutures, focusing on genes involved in vascularization. Tensile force upregulated expression of vascular factors, such as vascular endothelial growth factor (Vegf) and endothelial cell markers, in sutures within 3 h. The expression of connective tissue growth factor (Ctgf) and Rho-associated coiled-coil containing protein kinase 2 (Rock2) was also upregulated by tensile force. A CTGF-neutralizing antibody and the ROCK inhibitor, Y-27632, abolished tensile-force-induced Vegf expression. Moreover, tensile force activated extracellular signal-related kinase 1/2 (ERK1/2) signaling in sagittal sutures, and the ERK1/2 inhibitor, U0126, partially inhibited tensile-force-induced Ctgf expression. These results indicate that tensile force induces in vivo gene expression associated with vascularization early in tensile-force-induced sutural bone formation. Moreover, the early induction of Vegf gene expression is regulated by CTGF and ROCK2.

Mechanical forces induce odontoblastic differentiation of mesenchymal stem cells on three-dimensional biomimetic scaffolds.

The mechanical induction of cell differentiation is well known. However, the effect of mechanical compression on odontoblastic differentiation remains to be elucidated. Thus, we first determined the optimal conditions for the induction of human dental pulp stem cells (hDPSCs) into odontoblastic differentiation in response to mechanical compression of three-dimensional (3D) scaffolds with dentinal tubule-like pores. The odontoblastic differentiation was evaluated by gene expression and confocal laser microscopy. The optimal conditions, which were: cell density, 4.0 × 105 cells/cm2 ; compression magnitude, 19.6 kPa; and loading time, 9 h, significantly increased expression of the odontoblast-specific markers dentine sialophosphoprotein (DSPP) and enamelysin and enhanced the elongation of cellular processes into the pores of the membrane, a typical morphological feature of odontoblasts. In addition, upregulation of bone morphogenetic protein 7 (BMP7) and wingless-type MMTV integration site family member 10a (Wnt10a) was observed. Moreover, the phosphorylation levels of mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 were also enhanced by mechanical compression, indicating the involvement of the MAPK signalling pathway. It is noteworthy that human mesenchymal stem cells (MSCs) derived from bone marrow and amnion also differentiated into odontoblasts in response to the optimal mechanical compression, demonstrating the importance of the physical structure of the scaffold in odontoblastic differentiation. Thus, odontoblastic differentiation of hDPSCs is promoted by optimal mechanical compression through the MAPK signalling pathway and expression of the BMP7 and Wnt10a genes. The 3D biomimetic scaffolds with dentinal tubule-like pores were critical for the odontoblastic differentiation of MSCs induced by mechanical compression. Copyright © 2014 John Wiley & Sons, Ltd.