Kyung-Ku Lee

Anodic oxidized nanotubular titanium implants enhance bone morphogenetic protein-2 delivery

Implant failure has been attributed to loosening of an implant from the host bone possibly due to poor osseointegration. One promising strategy for improving osseointegration is to develop a functional implant surface that promotes osteoblast differentiation. In this study, a titanium (Ti) surface was functionalized by an anodic oxidation process and was loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2). The following four groups of Ti surfaces were prepared: machined (M), anodized machined (MA), resorbable blast medium (RBM), and anodized RBM (RBMA). The surfaces were characterized by scanning electron microscopy and contact angle measurements. The results showed that a Ti oxide layer (TiO(2)) was observed in the anodized surfaces in the form of nanotubes, approximately 100 nm in diameter and 500 nm in length. The hydrophilic properties of the anodized surfaces were significantly improved. The adsorbed rhBMP-2 loaded on the nonanodized surfaces and lyophilized showed spherical particle morphology. However, the adsorbed rhBMP-2 showed a dispersed pattern over the anodized surfaces. The velocity of the rhBMP-2 released from the surfaces was measured to determine if the anodized surface can improve in delivery efficiency. The results showed that the release velocity of the rhBMP-2 from the anodized surfaces was sustained when compared with that of the nonanodized surfaces. In addition, the rhBMP-2 released from the surface was found to be bioactive according to the alkaline phosphatase activity and the level of calcium mineral deposition. These results suggest that the TiO(2) nanotubular structure formed by anodizing is a promising configuration for sustained rhBMP-2 delivery.

Fabrication and characterization of functionally graded nano‐micro porous titanium surface by anodizing

The purpose of this study was to fabricate and characterize nanotubular structure on machined titanium (MA) and resorbable blast media (RBM) treated titanium by anodizing. The anodized MA and RBM were characterized with scanning electron microscopy, transmission electron microscopy, X-ray diffraction, energy disperse spectra, X-ray photoelectron spectra, and nano-indentation and scratch test. Highly ordered nanotubular layers of individually 100 nm in diameter and 500 nm in length approximately were formed regardless of the substrates. The nanotubular layers consisted mainly of amorphous TiO(2) with trace fluorine. The nanotubular surfaces on both the substrates significantly reduced water contact angles and elastic modulus compared with those prior to anodizing. The anodizing treatment significantly increased the surface roughness of the smooth MA, but significantly decreased the surface roughness of the roughened RBM. The critical delamination forces of the nanotubular layer were not obtained due to the limitation of surface roughness. The anodized RBM consisted of a nano-micro porous graded structure, or a nanotubular amorphous fluoride containing TiO(2) layer on top of micro-roughened titanium surface, which is expected to significantly improve the surface area that can be used to deliver drugs and growth factors and alleviate the interfacial elastic modulus mismatch as to enhance osseointegration when compared with conventional dental and orthopedic implant devices with smooth or acid etched surface.

Lactone form 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase inhibitors (statins) stimulate the osteoblastic differentiation of mouse periodontal ligament cells via the ERK pathway

BACKGROUND AND OBJECTIVE Recent studies reported that the lactone forms of 3-hydroxy- 3-methylglutaryl-coenzyme A reductase inhibitors, which are also known as statins, have a bone stimulatory effect. However, there are few reports on the effect of statins on periodontal ligament cells. This study examined the statin-induced osteoblastic differentiation of mouse periodontal ligament cells as well as its mechanism. MATERIAL AND METHODS Mouse periodontal ligament cells were cultured with lovastatin or simvastatin, and their viability was measured. The levels of alkaline phosphatase (ALP), osteocalcin, bone sialoprotein and bone morphogenetic protein-2 mRNA expression were evaluated by RT-PCR. The osteoblastic differentiation was characterized by the ALP activity and Alizarin Red-S staining for calcium deposition. The activity of the osteocalcin gene (OG2) and synthetic osteoblast-specific elements (6× OSE) promoter with statins was also measured using a luciferase assay. For the signal mechanism of statins, the ERK1/2 MAPK activity was determined by western blot analysis. RESULTS A statin treatment at concentrations < 1 μM did not affect the cell viability. Lovastatin or simvastatin at 0.1 μM increased the levels of ALP, osteocalcin, bone sialoprotein and bone morphogenetic protein-2 mRNA in mouse periodontal ligament cells. In addition, the ALP activity, mineralized nodule formation and OG2 and OSE promoter activity were higher in the lovastatin- or simvastatin-treated cells than the control cells. Western blot analysis confirmed that the statins stimulated the phosphorylation of ERK1/2. CONCLUSION Lovastatin and simvastatin may stimulate the osteoblastic differentiation of periodontal ligament cells via the ERK1/2 pathway. This suggests that the statins may be useful for regenerating periodontal hard tissue.

Effect of metal chloride solutions on coloration and biaxial flexural strength of yttria-stabilized zirconia

The effect of three kinds of transition metal dopants on the color and biaxial flexural strength of zirconia ceramics for dental applications was evaluated. Presintered zirconia discs were colored through immersion in aqueous chromium, molybdenum and vanadium chloride solutions and then sintered at 1450 °C. The color of the doped specimens was measured using a digital spectrophotometer. For biaxial flexural strength measurements, specimens infiltrated with 0.3 wt% of each aqueous chloride solution were used. Uncolored discs were used as a control. Zirconia specimens infiltrated with chromium, molybdenum and vanadium chloride solutions were dark brown, light yellow and dark yellow, respectively. CIE L*, a*, and b* values of all the chromium-doped specimens and the specimens infiltrated with 0.1 wt% molybdenum chloride solution were in the range of values for natural teeth. The biaxial flexural strengths of the three kinds of metal chloride groups were similar to the uncolored group. These results suggest that chromium and molybdenum dopants can be used as colorants to fabricate tooth colored zirconia ceramic restorations.

Effect of magnesium and calcium phosphate coatings on osteoblastic responses to the titanium surface

PURPOSE The aim of this study was to evaluate the surface properties and in vitro bioactivity to osteoblasts of magnesium and magnesium-hydroxyapatite coated titanium. MATERIALS AND METHODS Themagnesium (Mg) and magnesium-hydroxyapatite (Mg-HA) coatings on titanium (Ti) substrates were prepared by radio frequency (RF) and direct current (DC) magnetron sputtering.The samples were divided into non-coated smooth Ti (Ti-S group), Mg coatinggroup (Ti-Mg group), and Mg-HA coating group (Ti-MgHA group).The surface properties were evaluated using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The surface roughness was evaluated by atomic force microscopy (AFM). Cell adhesion, cell proliferation and alkaline phosphatase (ALP) activity were evaluated using MC3T3-E1 cells. Reverse transcription polymerase chain reaction (RT-PCR) analysis was performed. RESULTS Cross-sectional SEM images showed that Mg and Mg-HA depositionson titanium substrates were performed successfully. The surface roughness appeared to be similaramong the three groups. Ti-MgHA and Ti-Mg group had improved cellular responses with regard to the proliferation, alkaline phosphatase (ALP) activity, and bone-associated markers, such as bone sialoprotein (BSP) and osteocalcin (OCN) mRNA compared to those of Ti-S group. However, the differences between Ti-Mg group and Ti-MgHA group were not significant, in spite of the tendency of higher proliferation, ALP activity and BSP expression in Ti-MgHA group. CONCLUSION Mg and Mg-HAcoatings could stimulate the differentiation into osteoblastic MC3T3-E1 cells, potentially contributing to rapid osseointegration.

Design, synthesis of methotrexate-diosgenin conjugates and biological evaluation of their effect on methotrexate transport-resistant cells

A series of methotrexate-diosgenin conjugates was designed and synthesized to enhance the passive internalization of methotrexate (MTX) into transport-resistant cells. The inhibitory effects of these conjugates on dihydrofolate reductase (DHFR), and their anti-proliferation behaviors against a transport-resistant breast cancer cell line, MDA-MB-231, were investigated. All of the synthesized conjugates retained an ability to inhibit DHFR after the diosgenin substitution. The MTX conjugates were much more potent against methotrexate-resistant MDA-MB-231 cells than MTX. Conjugate 18, containing a disulfide bond, exhibited the most potent anti-proliferative and DHFR inhibitory effects (IC50=4.1μM and 17.21nM, respectively). Anti-proliferative activity was higher in the conjugate with a longer space linker (conjugate 21) than those with shorter linkers (conjugates 19 and 20). These results suggest that diosgenin conjugation of MTX may be an effective way to overcome its transport resistance in cancer cells.

Behavior of Osteoblast-Like Cells on a β-Tricalcium Phosphate Synthetic Scaffold Coated With Calcium Phosphate and Magnesium.

Objectives:Tricalcium phosphate (TCP) is one of the most useful synthetic scaffolds for bone grafts and has several advantages. However, the rapid degradation of TCP makes it less osteoconductive than the other candidates, and represents a major shortcoming. To overcome this problem, the authors investigated magnesium (Mg) and/or hydroxyapatite (HA) coating on a &bgr;-TCP substrate using a sputtering technique. Methods:Biocompatibility tests were carried out on &bgr;-TCP discs that were either uncoated (TCP), coated with HA by radio frequency magnetron sputtering (HA-TCP), coated with Mg by DC sputtering (Mg-TCP), or multicoated with Mg and HA by DC and radio frequency magnetron sputtering (MgHA-TCP). Results:Cells showed similar morphology in all 4 groups, and were widely spread, had flattened elongated shapes, and were connected to adjacent cells by pseudopods. An MTT assay revealed higher cell proliferation on HA-TCP, Mg-TCP, and MgHA-TCP compared with TCP at 3 and 5 days. MgHA-TCP also showed significantly higher alkaline phosphatase activity levels compared with TCP, HA-TCP, and Mg-TCP (P < 0.05). Conclusions:Results suggest that Mg-coated &bgr;-TCP could have great potential as a bone graft material for future applications in hard tissue regeneration.

Surface Characteristics of Oxide Film Prepared on CP Ti and Ti-10Ta-10Nb Alloy by Anodizing

In the present study, we investigated the formation of self-organized nanostructure oxide layers on CP Ti and Ti-10Ta-10Nb alloy in an electrolyte of 1M phosphoric acid and 1.5 wt% Hydrofluoric acid. The morphology of oxide film on substrate was observed using scanning electron microscopy and transmission electron microscopy The surface roughness of titanium oxide film was analyzed by atomic force microscopy and the crystalline of specimen was investigated using X-ray diffractometer. The results of this study showed that well-aligned titanium oxide nanotubes are formed with diameter of approx. 100nm and length of approx. 500nm with CP Ti. However, it is clear that TiTaNb alloy highly irregular structure with various diameters. Transmission electron microscope investigations show that the specimens were confirmed as amorphous. Such titanium oxide nanotubes are expected a well-adhered bioacitive surface layer on titanium substrate for orthopedics and dental implants.

Characteristics of Ir-Re Thin Films on WC for Lens Glass Molding by Ion Beam Assisted DC Magnetron Sputtering

Ir-Re thin films with Ti interlayer were deposited onto the tungsten carbide substrate by ion beam assisted DC magnetron sputtering. The Ir-Re films were prepared with targets of having two atomic percent of 7:3 and 5:5. The microstructure and surface analysis of the specimen were conducted by using SEM, XRD and AFM. Mechanical properties such as hardness and adhesion strength of Ir-Re thin film also were examined. The interlayer of pure titanium was formed with 100 nm thickness. The film growth of Ir-30at.%Re was faster than that of Ir-50at.%Re in the same deposition conditions. Ir-Re thin films consisted of dense and columnar structure irrespective of the different target compositions. The values of hardness and adhesion strength of Ir-30at.%Re thin film coated on WC substrate were higher than those of Ir-50at.%Re thin film.

Effects of Nb Addition on Corrosion Resistance and Cytotoxicity Behavior of Ti Alloys

The corrosion resistance and cytotoxicity behavior of Ti alloys were studied as a function of Nb contents(3wt.%Nb, 20wt.%Nb, 40wt.%Nb). Ti-Nb alloys were melted by vacuum arc furnace and then rolled to 50% reduction ratio after homogenized at 105 for 24hrs. The corrosion resistance of Ti-Nb alloys were investigated by potentiodynamic polarization test in the 0.9% NaCl and 5% HCI solution. Biocompatibility of Ti-Nb alloys was evaluated by cytotoxicity test. The results can be summarized as follows 1) The microstructure change from equiaxial to acicular and the increased phase in Ti-Nb alloys were obtained as the Nb content increased. 2) For the corrosion test in the solution of 0.9% NaCl and 5% HCI, the corrosion behavior of Ti-Nb alloys was similar to ASTM grade 2 CP Ti. 3) For the cytotoxicity test, Ti-Nb alloys showed excellent biocompatibility compared to ASTM grade 2 CP Ti, 316L STS and Co-Cr alloys.