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The aim of this study was to develop a three-dimensional porous bone graft material as vehicle for simvastatin delivery and to investigate its effect on primary human osteoblasts from three donors. Highly porous titanium dioxide (TiO2) scaffolds were submerged into simvastatin containing alginate solution. Microstructure of scaffolds, visualized by scanning electron microscopy and micro-computed tomography, revealed an evenly distributed alginate layer covering the surface of TiO2 scaffold struts. Progressive and sustained simvastatin release was observed for up to 19 days. No cytotoxic effects on osteoblasts were observed by scaffolds with simvastatin when compared to scaffolds without simvastatin. Expression of osteoblast markers (collagen type I alpha 1, alkaline phosphatase, bone morphogenetic protein 2, osteoprotegerin, vascular endothelial growth factor A and osteocalcin) was quantified using real-time reverse transcriptase-polymerase chain reaction. Secretion of osteoprotegerin, vascular endothelial growth factor A and osteocalcin was analysed by multiplex immunoassay (Luminex). The relative expression and secretion of osteocalcin was significantly increased by cells cultured on scaffolds with 10 µM simvastatin when compared to scaffolds without simvastatin after 21 days. In addition, secretion of vascular endothelial growth factor A was significantly enhanced from cells cultured on scaffolds with both 10 nM and 10 µM simvastatin when compared to scaffolds without simvastatin at day 21. In conclusion, the results indicate that simvastatin-coated TiO2 scaffolds can support a sustained release of simvastatin and induce osteoblast differentiation. The combination of the physical properties of TiO2 scaffolds with the osteogenic effect of simvastatin may represent a new strategy for bone regeneration in defects where immediate load is wanted or unavailable.

The aim of this study was to show that cathodic polarization can be used for coating commercial implant surfaces with an immobilized but functional and bioavailable surface layer of strontium (Sr). Moreover, this study assessed the effect of fluorine on Sr-attachment. X-ray photoelectron spectroscopy revealed that addition of fluorine (F) to the buffer during coating increased surface Sr-amounts but also changed the chemical surface composition by adding SrF2 alongside of SrO whereas pre-treatment of the surface by pickling in hydrofluoric acid appeared to hinder Sr-attachment. Assessment of the bio-availability hinted at a positive effect of Sr on cell differentiation given that the surface reactivity of the original surface remained unchanged. Additional SrF2 on the surface appeared to reduce undesired surface contamination while maintaining the surface micro-topography and micro-morphology. Anyhow, this surface modification revealed to create nano-nodules on the surface.

The aim of this study was to investigate the effect of TiO2 scaffold (SC) coated with an alginate hydrogel containing a proline-rich peptide (P2) on osteoblast proliferation and differentiation in vitro. Peptide release was evaluated and a burst release was observed during the first hours of incubation, and then progressively released overtime. No changes were observed in the cytotoxicity after 48 h of seeding MC3T3-E1 cells on the coated and uncoated TiO2 SC. The amount of cells after 7 days was higher on uncoated TiO2 SC than on alginate-coated TiO2 SC, measured by DNA content and scanning electron microscope imaging. In addition, while lower expression of integrin beta1 was detected for alginate-coated TiO2 SC at this time point, similar gene expression was observed for other integrins, fibronectin-1, and several osteoblast differentiation markers. After 21 days, gene expression of integrin beta3, fibronectin-1, osterix, and collagen-I was increased in alginate-coated compared to TiO2 SC. Moreover, increased gene expression of integrin alpha8, bone morphogenetic protein 2, interleukin-6, and collagen-I was found on P2 alginate-coated TiO2 SC compared to alginate-coated TiO2 SC. In conclusion, our results indicate that alginate-coated TiO2 SC can act as a matrix for delivery of proline-rich peptides increasing osteoblast differentiation. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013., (Copyright © 2012 Wiley Periodicals, Inc.)

This study aimed at the investigation of the effect of zirconium dioxide (ZrO2) addition on the mechanical properties of titanium dioxide (TiO2) bone scaffolds. The highly biocompatible TiO2 has been identified as a promising material for bone scaffolds, whereas the more bioinert ZrO2 is known for its excellent mechanical properties. Ultra-porous TiO2 scaffolds (>89% porosity) were produced using polymer sponge replication with 0-40 wt.% of the TiO2 raw material substituted with ZrO2. Microstructure, chemical composition, and pore architectural features of the prepared ceramic foams were characterised and related to their mechanical strength. Addition of 1 wt.% of ZrO2 led to 16% increase in the mean compressive strength without significant changes in the pore architectural parameters of TiO2 scaffolds. Further ZrO2 additions resulted in reduction of compressive strength in comparison to containing no ZrO2. The appearance of zirconium titanate (ZrTiO4) phase was found to hinder the densification of the ceramic material during sintering resulting in poor intergranular connections and thus significantly reducing the compressive strength of the highly porous ceramic foam scaffolds., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Introduction: The aims of this study were to calculate the volume of white spot lesions by using microcomputed tomography and to determine which clinical attribute of the white spot lesion could better predict its volume: the clinically visible white spot lesion surface area or its color intensity., Methods: White spot lesions were induced in 8 patients in vivo on 23 healthy premolars destined for extraction during orthodontic treatment by using specially designed plaque-retaining orthodontic bands. After 7 weeks, the premolars were extracted. After extraction, the resulting white spot lesions were photographed and clinically graded. The teeth were analyzed with microcomputed tomography., Results: After 7 weeks, 70% of the teeth developed clinical white spot lesions. Clinically, the size of the lesions varied from minor to severe. Their volumes varied from 0 to 1.2931 mm(3). The traditional grades for white spot lesions correlated significantly with color intensity. A significant correlation was found between white spot lesion color intensity and lesion volume. This correlation was found to be better than that between the white spot lesion clinical score and lesion volume., Conclusions: Our results indicate that white spot lesion color intensity might predict the depth of enamel demineralization as well as or better than traditional white spot lesion scoring. Therefore, the dentist could use this information when planning treatment for white spot lesions., (Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.)

The osteoconductive capacity of TiO(2) scaffolds was investigated by analysing the bone ingrowth into the scaffold structure following their placement into surgically modified extraction sockets in Gottingen minipigs. Non-critical size defects were used in order to ensure sufficient bone regeneration for the evaluation of bone ingrowth to the porous scaffold structure, and sham sites were used as positive control. Microcomputed tomographic analysis revealed 73.6±11.1% of the available scaffold pore space to be occupied by newly formed bone tissue, and the volumetric bone mineral density of the regenerated bone was comparable to that of the native cortical bone. Furthermore, histological evidence of vascularization and the presence of bone lamellae surrounding some of the blood vessels were also observed within the inner regions of the scaffold, indicating that the highly interconnected pore structure of the TiO(2) scaffolds supports unobstructed formation of viable bone tissue within the entire scaffold structure. In addition, bone tissue was found to be in direct contact with 50.0±21.5% of the TiO(2) struts, demonstrating the good biocompatibility and osteoconductivity of the scaffold material., (Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Despite being considered noncritical size defects, extraction sockets often require the use of bone grafts or bone graft substitutes in order to facilitate a stable implant site with an aesthetically pleasing mucosal architecture and prosthetic reconstruction. In the present study, the effect of novel TiO(2) scaffolds on dimensional ridge preservation was evaluated following their placement into surgically modified extraction sockets in the premolar region of minipig mandibles. After six weeks of healing, the scaffolds were wellintegrated in the alveolar bone, and the convex shape of the alveolar crest was preserved. The scaffolds were found to partially preserve the dimensions of the native buccal and lingual bone walls adjacent to the defect site. A tendency towards more pronounced vertical ridge resorption, particularly in the buccal bone wall of the nongrafted alveoli, indicates that the TiO(2) scaffold may be used for suppressing the loss of bone that normally follows tooth extraction.

The current study compares biocompatibility, cell growth and morphology, pore diameter distribution, and interconnectivity of a novel titanium dioxide (TiO(2)) bone graft substitute granules with three different commercially available bone graft granules Natix, Straumann BoneCeramic, and Bio-Oss. Human primary mesenchymal stem cells were cultured on the bone graft substitutes and cell viability and proliferation were evaluated after 1 and 3 days. The microstructural properties of the bone graft substitutes were evaluated by scanning electron microscopy, micro-computed tomography analysis, and mechanical testing. The cell viability and proliferation, porosity, interconnectivity, open pore size, and surface area-to-volume ratio of TiO(2) granules were significantly higher than commercial bone granules (Bio-Oss and Straumann BoneCeramic).

Highly porous and well interconnected titanium dioxide (TiO(2)) scaffolds with compressive strength above 2.5 MPa were fabricated without compromising the desired pore architectural characteristics, such as high porosity, appropriate pore size, surface-to-volume ratio, and interconnectivity. Processing parameters and pore architectural characteristics were investigated in order to identify the key processing steps and morphological properties that contributed to the enhanced strength of the scaffolds. Cleaning of the TiO(2) raw powder removed phosphates but introduced sodium into the powder, which was suggested to decrease the slurry stability. Strong correlation was found between compressive strength and both replication times and solid content in the ceramic slurry. Increase in the solid content resulted in more favourable sponge loading, which was achieved due to the more suitable rheological properties of the ceramic slurry. Repeated replication process induced only negligible changes in the pore architectural parameters indicating a reduced flaw size in the scaffold struts. The fabricated TiO(2) scaffolds show great promise as load-bearing bone scaffolds for applications where moderate mechanical support is required.