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This study investigated the in vivo osteoblast and osteoclast gene expression in the peri-implant bone tissue of the strontium (Sr)-incorporated microstructured Ti implants (SLA/Sr) in order to evaluate whether local Sr delivery to the implant surface as in the form of SrTiO3 also exerts original bone healing enhancement effect of Sr that take place through the dual modes of action of a stimulation of osteogenesis and an inhibition of osteoclastogenesis. The in vivo mRNA expression of osteoblast- and osteoclast-related genes in the peri-implant bone and removal torque forces of the SLA/Sr implants were compared with a chemically modified super-hydrophilic SLA implants (SLActive®) in rabbit cancellous bone after 2 weeks of implantation. There was no significant difference in the removal torque values between the two groups. Both the torque-tested SLA/Sr and SLActive implants exhibited a considerable quantity of bone attached to the surface. Real-time PCR analysis revealed notably increased mRNA expression of osteoblast genes (Runx2, osterix and osteocalcin) in the peri-implant bone of the SLA/Sr implants compared with the SLActive implants ( p < 0.05), whereas osteoclast phenotype gene (TRAP) expression was markedly decreased in the SLA/Sr implant ( p < 0.05). The results at the molecular level suggest that local Sr delivery as in the form of the Sr-incorporated Ti oxide layer favors early osseointegration of microrough Ti implants via a positive modulation of bone healing, that is, a promotion of osteoblast differentiation and suppression of osteoclastogenesis, in the bone-implant interface of cancellous bone. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A:298-306, 2013. [ABSTRACT FROM AUTHOR]

Strontium (Sr) has been successfully used for the treatment of osteoporotic bone, increasing new bone formation while reducing bone resorption by stimulating proliferation and differentiation of osteoblastic cells and inhibiting osteoclast function. In this study, Sr-incorporated Ti oxide layer was produced on clinically relevant osteoconductive implant surface, that is, a grit-blasted microrough Ti surface, by a simple hydrothermal treatment with the expectation of utilizing the osteoblast response enhancement effect of Sr for the future applications as a more osteoconductive surface of the permanent load-bearing endosseous implants, without altering the original microrough surface features of grit-blasted Ti at the micron-scale. This surface exhibits a hierarchical structure (i.e., a nanoscale surface architecture of the Sr-incorporated Ti oxide layer (SrTiO3) imposed on micron-scale rough Ti structure) and Sr ion release into physiological solution. In vitro experiments using primary mouse bone marrow stromal cells (BMSCs) revealed that the hydrothermally produced SrTiO3 coating promotes both the early and late cell response of BMSCs grown on a microrough Ti surface, with notably enhanced attachment, spreading, focal adhesion, alkaline phosphatase activity, and expression of critical integrins and osteoblastic phenotype genes. These results indicate that a hydrothermally produced SrTiO3 coating improves the osteoconductivity of the microrough Ti surface by enhancing both the early and late cell response of BMSCs. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012. [ABSTRACT FROM AUTHOR]

This study investigated the effects of magnesium ion (Mg) incorporation into the surface of deproteinized porcine cancellous bone in the bone healing of rabbit calvarial defects with the expectation of utilizing the integrin-ligand binding enhancement effect of Mg, and compared its bone healing capacity with that of untreated porcine cancellous bone and deproteinized bovine bone (Bio-Oss). Hydrothermal treatment was performed to produce Mg-incorporated porcine bone using an alkaline Mg-containing solution. The surface morphology and chemical composition of the samples were investigated using scanning electron microscopy, energy-dispersive X-ray spectrometry, and X-ray photoelectron spectroscopy. Defects 7 mm in diameter were created in the calvaria of 14 adult male New Zealand White rabbits and were filled with (1) untreated porcine bone (PB), (2) Bio-Oss, and (3) Mg-containing porcine bone (MG). The percentage of newly formed bone (NB%) was evaluated histomorphometrically at 2 and 4 weeks after implantation. Hydrothermal treatment resulted in a Mg-containing surface in porcine bone covered with nanostructures ∼100 nm in size. The MG group supported better new bone formation compared with the other groups. Osteoconductive new bone formation was observed in the central defect area in the MG group at an early healing time-point. Histomorphometric analysis revealed significantly greater NB% in the MG group when compared with the untreated PB and Bio-Oss groups at 4 weeks ( p < 0.05). The Mg-incorporated porcine bone with surface nanostructures achieved rapid new bone formation in the osseous defects of rabbit calvaria compared with untreated xenografts of porcine and bovine origin. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012. [ABSTRACT FROM AUTHOR]

Metallic implantation materials having high yield strength, low elastic modulus, and non-cytotoxic alloying elements would be advantageous for the long-term stability of implants. This study assessed the surface and mechanical properties, and also in vitro osteoconductivity of ultrafine-grained (UFG) Ti-13Nb-13Zr alloy produced by dynamic globularization without any severe deformation for future biomedical applications as an endosseous implant material. The surface characteristics and mechanical properties were investigated by orientation image microscopy, contact angle measurements, optical profilometry, and uniaxial tension tests. Mouse calvaria-derived pre-osteoblastic cell (MC3T3-E1) attachment, spreading, viability, alkaline phosphatase (ALP) activity, and quantitative analysis of osteoblastic gene expression on UFG Ti-13Nb-13Zr alloy were compared with coarse-grained (CG) Ti-13Nb-13Zr and CG Ti-6Al-4V alloys. Dynamic globularized Ti-13Nb-13Zr alloy has an ultrafine grain size (0.3 μm) and an excellent combination of yield strength and elastic modulus compared with CG alloys, which displayed significantly lower water contact angles compared with CG alloys ( P<0.05). The UFG and CG Ti-13Nb-13Zr alloys displayed significantly increased cellular attachment compared with CG Ti-6Al-4V alloy ( P<0.05). The UFG Ti-13Nb-13Zr supported better cell spreading and more numerous focal adhesions. ALP activity ( P<0.05) and mRNA expressions of the osteoblast transcription factor genes (osterix, Runx2) and marker gene for osteoblast differentiation (osteocalcin) were markedly increased in cells grown on the UFG substrate compared with CG substrates at early incubation timepoints. Enhanced pre-osteoblast response to UFG Ti-13Nb-13Zr substrate is attributable to the non-cytotoxic alloying elements and the submicron scale grain size contributes to the superior surface hydrophilicity and abundant grain boundaries favorable for cell behavior. These findings indicate that dynamic globularized UFG Ti-13Nb-13Zr alloy is promising for load-bearing endosseous implant material because of excellent mechanical and biological compatibilites. Park CH, Lee CS, Kim Y-J, Jang J-H, Suh J-Y, Park J-W. Improved pre-osteoblast response and mechanical compatibility of ultrafine-grained Ti-13Nb-13Zr alloy. Clin. Oral Impl. Res. , 2011; 735-742 doi: 10.1111/j.1600-0501.2010.02053.x [ABSTRACT FROM AUTHOR]

Objective: This study investigated the surface characteristics and in vitro osteoconductivity of a titanium (Ti) surface incorporated with the magnesium ions (Mg) produced by hydrothermal treatment for future application as an endosseous implant surface. Material and methods: Mg-incorporated Ti oxide surfaces were produced by hydrothermal treatment using Mg-containing solution on two different microstructured surfaces - abraded minimally rough (Ma) or grit-blasted moderately rough (RBM) samples. The surface characteristics were evaluated using scanning electron microscopy, thin-film X-ray diffractometry, X-ray photoelectron spectroscopy, optical profilometry, and inductively coupled plasma atomic emission spectroscopy (ICP-AES). MC3T3-E1 pre-osteoblast cell attachment, proliferation, alkaline phosphatase (ALP) activity, and quantitative analysis of osteoblastic gene expression on Ma, RBM, Mg-incorporated Ma (Mg), and Mg-incorporated grit-blasted (RBM/Mg) Ti surfaces were evaluated. Results: Hydrothermal treatment produced an Mg-incorporated Ti oxide layer with nanoporous surface structures. Mg-incorporated surfaces showed surface morphologies and surface roughness values almost identical to those of untreated smooth or micro-rough surfaces at the micron scale. ICP-AES analysis showed Mg ions released from treated surfaces into the solution. Mg incorporation significantly increased cellular attachment ( P=0 at 0.5 h, P=0.01 at 1 h) on smooth surfaces, but no differences were found on micro-rough surfaces. Mg incorporation further increased ALP activity in cells grown on both smooth and micro-rough surfaces at 7 and 14 days of culture ( P=0). Real-time polymerase chain reaction analysis showed higher mRNA expressions of the osteoblast transcription factor gene (Dlx5), various integrins, and the osteoblast phenotype genes (ALP, bone sialoprotein and osteocalcin) in cells grown on micro-rough (RBM) and Mg-incorporated (Mg and RBM/Mg) surfaces than those on Ma surfaces. Mg incorporation further increased the mRNA expressions of key osteoblast genes and integrins (α1, α2, α5, and β1) in cells grown on both the smooth and the micro-rough surfaces. Conclusion: These results indicate that an Mg-incorporated nanoporous Ti oxide surface produced by hydrothermal treatment may improve implant bone healing by enhancing the attachment and differentiation of osteoblastic cells. To cite this article: Park J-W, Kim Y-J, Jang J-H, Song H. Osteoblast response to magnesium ion-incorporated nanoporous titanium oxide surfaces. Clin. Oral Impl. Res. 21, 2010; 1278-1287. doi: 10.1111/j.1600-0501.2010.01944.x [ABSTRACT FROM AUTHOR]

Objective: This study investigated the surface characteristics and in vitro biocompatibility of titanium (Ti) surfaces incorporated with strontium ions (Sr) and/or phosphate ions (P) produced by hydrothermal treatment for future applications as endosseous implant surfaces. Material and methods: Sr and/or P-incorporated Ti oxide surfaces were produced by hydrothermal treatment. The surface characteristics were evaluated by scanning electron microscopy, thin-film X-ray diffractometry, X-ray photoelectron spectroscopy, contact angle and surface energy measurements, inductively coupled plasma atomic emission spectroscopy, and profilometry. MC3T3-E1 pre-osteoblast cell attachment, morphology of spread cells, viability, and quantitative analysis of osteoblastic gene expression on grit-blasted microrough (RBM), P-incorporated (P), and P- and Sr-incorporated (SrP) Ti surfaces were evaluated. Results: Microstructured P and SrP surfaces showed significantly higher wettability and surface energy compared with RBM surfaces ( P<0.01). After immersion in Hank's balanced salt solution, considerable apatite deposition was observed on the P and SrP surfaces. Sr incorporation significantly increased cellular attachment and viability compared with other surfaces ( P<0.05). Real-time polymerase chain reaction analysis showed markedly higher mRNA expressions of the osteoblast transcription factor gene (Runx2) and the osteoblast phenotype genes (alkaline phosphatase, osteopontin, bone sialoprotein, and osteocalcin) in cells grown on the P and SrP surfaces compared with those on the RBM surface. Conclusions: These results demonstrate that Sr- and P-incorporated Ti oxide surfaces may improve implant bone healing by enhancing attachment, viability, and differentiation of osteoblastic cells. To cite this article: Park J-W, Kim Y-J, Jang J-H. Enhanced osteoblast response to hydrophilic strontium and/or phosphate ions-incorporated titanium oxide surfaces. Clin. Oral Impl. Res. 21, 2010; 398–408. doi: 10.1111/j.1600-0501.2009.01863.x [ABSTRACT FROM AUTHOR]

Objectives: This study investigated the efficacy of new bone graft substitutes – biphasic calcium phosphates (BCP) made of submicron-sized grains with fully interconnected wide-range micron-scale pores in two different macrodesigns: donut shaped with a 300–400 μm central macropore (n-BCP-1) or rod-shaped (n-BCP-2) – in the healing of rabbit calvarial defects, and compared their bone-healing properties with those of various commercial bone substitutes, which included substitutes with similar BCP composition (MBCP and Osteon), anorganic bovine bone (Bio-Oss), and β-TCP (Cerasorb). Material and methods: The surface morphology of the bone substitutes was investigated using scanning electron microscopy (SEM). Defects 8 mm in diameter were created in the calvaria of 30 adult male New Zealand White rabbits and were filled with six types of bone substitutes. The percentage of newly formed bone (NB%) was evaluated histomorphometrically 4 and 8 weeks after implantation. Results: SEM observation showed submicron-sized grains with fully interconnected micropore structures in the n-BCP-1 and n-BCP-2 groups; these groups also showed considerable new bone formation in inner micropores as well as on the outer surfaces. The n-BCP-1 group exhibited enhanced new bone formation and direct ingrowth of bone tissue with blood vessels into central pores. Histomorphometric analysis showed significantly greater NB% in the n-BCP-1 group when compared with the other groups at 4 and 8 weeks ( P<0.05). Conclusion: A new BCP ceramics made of submicron-sized grains with a hierarchical pore structure was an effective osteoconductive material for the treatment of osseous defects of rabbit calvaria. To cite this article: Park J-W, Kim E-S, Jang J-H, Suh J-Y, Park K-B, Hanawa T. Healing of rabbit calvarial bone defects using biphasic calcium phosphate ceramics made of submicron-sized grains with a hierarchical pore structure. Clin. Oral Impl. Res. 21, 2010; 268–276. doi: 10.1111/j.1600-0501.2009.01846.x [ABSTRACT FROM AUTHOR]

Objective: This histomorphometric study compared the efficacy of a new bone graft substitute (N-HA) derived from hen eggshell, consisted of submicron scale porous hydroxyapatite structure, in the healing of 8 mm diameter critical size defects in rat calvaria. We compared N-HA alone or in combination with calcium sulfate (CS), with a commercial bone substitute, anorganic bovine bone (Bio-Oss, BO). Material and methods: Critical size defects were created in calvaria of 56 adult Sprague–Dawley rats. Animals were divided into four groups and treated with (1) unfilled defects, (2) N-HA grafts, (3) BO grafts and (4) N-HA/CS grafts. The percentage of new bone formed (NB%) was evaluated histomorphometrically after 6 and 12 weeks. Results: The N-HA group exhibited more new bone formation compared with other groups at 6 and 12 weeks. Histomorphometric analysis showed greater NB% in N-HA group (11.2% at 4 weeks and 19.2% at 12 weeks) compared with those in unfilled (3.9% at 6 weeks and 6.4% at 12 weeks), BO-treated (6.4% at 6 weeks and 8.2% at 12 weeks) and N-HA/CS-treated (6.3% at 6 weeks and 12.6% at 12 weeks) groups. The N-HA group showed significant differences in NB% compared with unfilled group at 6 weeks ( P=0.016), unfilled and BO-treated groups at 12 weeks ( P=0.001). The addition of CS did not enhance the NB% compared with defects grafted with N-HA alone. Conclusion: N-HA was an osteoconductive bone substitute for treating osseous defects in critical size defects of rat calvaria. [ABSTRACT FROM AUTHOR]