Håvard Jostein Haugen

• Johnsen, Gaute Floer; Sunde, Pia Titterud & Haugen, Håvard Jostein (2018). Validation of contralateral premolars as the substrate for endodontic comparison studies. International Endodontic Journal.  ISSN 0143-2885.  51, s 942- 951 . doi: 10.1111/iej.12902 Fulltekst i vitenarkiv. Vis sammendrag

  AIM: To use micro-CT technology and metrology software to validate the use of contralateral premolars as samples in endodontic comparison studies by comparing them before and after canal instrumentation with one instrumentation system. Furthermore, to determine if contralateral premolar roots will yield non-significantly different outcomes regarding shaping ability (volume), degree of twisting, and three-dimensional shape changes. The null-hypothesis (H0 ) is that there are no differences between the contralateral premolar roots pre- or post-instrumentation. METHODOLOGY: Twenty-eight extracted human contralateral premolars (n=44 contralateral roots) from 12 donor patients were scanned with microcomputed tomography before and after instrumentation. Root canal lengths (RCL) were measured visually using a dental operating microscope, electronic apex locator, and micro-CT scans. Data were analyzed statistically for differences between pre- and post-instrumentation. RESULTS: Instrumentation increased the volume of the canals significantly (P<0.05). Degree of twisting for a majority (83%) of the contralateral roots pairs did not change significantly (P>0.05). There was no significant difference (P>0.05) in the shape deviation analysis between contralateral pairs. There was no significant difference (P>0.05) for root canal length between the contralateral pairs for any of the three endometric methods. CONCLUSION: Contralateral premolar root canals were associated with similar changes in terms of volume, three-dimensional shape, and degree of twisting from pre- to post-instrumentation. There was no difference between the contralateral premolar root pairs pre- and post-instrumentation, and the study validates contralateral premolars as samples for root canal comparison studies. The null-hypothesis (H0 ) could not be rejected. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

• Kamyar, Negin; Greenhalgh, Ryan; Nascimentoa, Tatiana R. L; Medeiros, Eliton S; Matthews, Peter D; Nogueira, Liebert Parreiras; Haugen, Håvard Jostein; Lewis, David J. & Blaker, Jonny j (2018). Exploiting Inherent Instability of 2D Black Phosphorus for Controlled Phosphate Release from Blow-Spun PLGA Nanofibers. ACS Applied Materials and Interfaces.  ISSN 1944-8244. . doi: 10.1021/acsanm.8b00938 Vis sammendrag

  Efforts have been made to stabilize black phosphorus (BP) to utilize its tunable band gap and anisotropic mechanical properties. Here, the intrinsic instability of BP is exploited for controlled therapeutic ion release, namely phosphate. BP was incorporated into degradable poly (lactide-co-glycolide) fibers via solution blow spinning. Raman spectroscopy confirmed the incorporation of 2D-BP into the nanocomposite along with ICP-AES. It was also demonstrated that modifying the initial loading of 2D-BP in the PLGA fibers permitted tunable release rates of phosphate ions over an 8 weeks in vitro study.

• Leire, Virto; Haugen, Håvard Jostein; Fernández-mateos, Pilar; Cano, Pilar; González, Jerián; Jiménez-ortega, Vanesa; Esquifino, Ana isabel & Sanz Alonso, Mariano (2018). Melatonin expression in periodontitis and obesity: An experimental in-vivo investigation. Journal of Periodontal Research.  ISSN 0022-3484.  s 1- 7 . doi: 10.1111/jre.12571 Fulltekst i vitenarkiv. Vis sammendrag

  Background and Objective: Melatonin deficiency has been associated with obesity and systemic inflammation. This study aims to evaluate whether melatonin could interfere with the mechanisms of co-morbidity linking obesity and periodontitis. Material and Methods: Twenty-eight male Wistar rats were randomly divided in 4 groups: control group (Con) (fed with standard diet); high-fat diet group (HFD) (fed with a diet containing 35.2% fat); Con group with induced periodontitis (Con-Perio) and HFD group with induced periodontitis (HFD-Perio). To induce periodontitis, the method of oral gavages with Porphyromonas gingivalis ATCC W83K1 and Fusobacterium nucleatum DMSZ 20482 was used. Circulating melatonin levels were analyzed by multiplex immunoassays. Periodontitis was assessed by alveolar bone loss (microcomputed tomography and histology) and by surrogate inflammatory outcomes (periodontal pocket depth, modified gingival index and plaque dental index). Results: Plasma melatonin levels were significantly decreased (P < .05) in the obese rats with periodontitis when compared with controls or with either obese or periodontitis rats. Alveolar bone loss increased 27.71% (2.28 µm) in HFD-Perio group compared with the Con group. The histological analysis showed marked periodontal tissue destruction with osteoclast activity, particularly in the HFD-Perio group. A significant negative correlation (P < .05) was found between periodontal pocket depth, modified gingival index and circulating melatonin levels. Conclusion: Obese and periodontitis demonstrated significantly lower melatonin concentrations when compared with controls, but in obese rats with periodontitis these concentrations were even significantly lower when compared with either periodontitis or obese rats. These results may indicate that melatonin deficiency could be a key mechanism explaining the co-morbidity effect in the association between obesity and periodontitis.

• Zhang, Xianbin; Tiainen, Hanna & Haugen, Håvard Jostein (2018). Comparison of titanium dioxide scaffold with commercial bone graft materials through micro-finite element modelling in flow perfusion. Medical and Biological Engineering and Computing.  ISSN 0140-0118. . doi: 10.1007/s11517-018-1884-2 Fulltekst i vitenarkiv. Vis sammendrag

  TiO2 scaffolds have previously shown to have promising osteoconductive properties in previous in vivo experiments. Appropriate mechanical stimuli can further promote this osteoconductive behaviour. However, the complex mechanical environment and the mechanical stimuli enhancing bone regeneration for porous bioceramics have not yet been fully elucidated. This paper aims to compare and evaluate mechanical environment of TiO2 scaffold with three commercial CaP biomaterials, i.e. Bio-Oss, Cerabone and Maxresorb under simulated perfusion culture conditions. The solid phase and fluid phase were modelled as linear elastic material and Newtonian fluid, respectively. The mechanical stimulus was analysed within these porous scaffolds quantitatively. The results showed that the TiO2 had nearly heterogeneous stress distributions, however lower effective Young’s modulus than Cerabone and Maxresorb. The permeability and wall shear stress (WSS) for the TiO2 scaffold was significantly higher than other commercial bone substitute materials. Maxresorb and Bio-Oss showed lowest permeability and local areas of very high WSS. The detailed description of the mechanical performance of these scaffolds could help researchers to predict cell behaviour and to select the most appropriate scaffold for different in vitro and in vivo performances.

• Barrantes Bautista, Alejandro; Wengenroth, Jonas; Arnebrant, Thomas & Haugen, Håvard Jostein (2017). Poly-L-lysine/heparin multilayer coatings prevent blood protein adsorption. Journal of Colloid and Interface Science.  ISSN 0021-9797.  485, s 288- 295 . doi: 10.1016/j.jcis.2016.09.046
• Cama, Giuseppe; Nkhwa, Shatani; Gharibi, Borzo; Lagazzo, Alberto; Cabella, Roberto; Carbone, Christina; Dubruel, Peter; Haugen, Håvard Jostein; Di Silvi, Lucy & Deb, Sanjukta (2017). The role of new zinc incorporated monetite cements on osteogenic differentiation of human mesenchymal stem cells. Materials Science and Engineering C: Materials for Biological Applications.  ISSN 0928-4931.  78, s 485- 494 . doi: 10.1016/j.msec.2017.04.086 Vis sammendrag

  β-Tricalcium phosphate particles were sintered in the presence of different amounts (0–0.72 mol) of zinc oxide (ZnO) to prepare zinc doped β-TCP (Znβ-TCP) particles for further use in novel monetite (DCPA: CaHPO4) zinc incorporated bone cements with osteogenic differentiation potential towards human mesenchymal stem cells (hMSCs). XRD analysis of zinc incorporated cements prepared with β-TCP reagent particles doped with different amount of ZnO (i.e. 0.03, 0.09 and 0.18 mol ZnO) revealed the presence of unreacted Znβ-TCP and monetite. Furthermore, it was shown that zinc ions preferentially occupied the β-TCP crystal lattice rather than the monetite one. Release experiments indicated a burst release of ions from the different fabricated cements during the first 24 h of immersion with zinc concentrations ranging between 85 and 100% of the total concentration released over a period of 21 days. Cell proliferation significantly increased (P < 0.05) on zinc incorporated monetite respect to control samples (Zinc-free cement) at 7 and 14 days post seeding. The expression of Runx-2 was significantly up regulated (P < 0.05) in the case of cells seeded on monetite prepared with β-TCP doped with 0.03 moles of ZnO. On the other hand, the cell mineralization as well as the expression of osteogenic marker genes ALP and OSC decreased significantly (P < 0.05) at 14 days post cell seeding. In conclusion, these results suggest that the zinc ions released from the cements during the first 24 h of culture played a critical role in regulating the osteogenic differentiation of hMSCs

• Hussain, Badra; Thieu, Minh Khai Le; Johnsen, Gaute Floer; Reseland, Janne Elin & Haugen, Håvard Jostein (2017). Can CAD/CAM resin blocks be considered as substitute for conventional resins?. Dental Materials.  ISSN 0109-5641.  33(12), s 1362- 1370 . doi: 10.1016/j.dental.2017.09.003 Vis sammendrag

  Objective Dentists are facing a myriad of new CAD/CAM product for dental filling therapies. Are the new materials any worthwhile using? Are they succeeding the standard filling materials? Here we compare for the first time the new resin-composite blocks (RCBs) with conventional materials (Filtek Z250 and Tetric EvoCeram). Methods The material were tested for residual monomer elution by HPLC, thermogravimetric analysis (TG) was used to determine the percentage of fillers by weight, hardness was evaluated by Vickers method, morphology of fillers and distribution in the matrix were examined by scanning electron microscopy (SEM), elemental analysis for elemental determination of the filler particles was performed by energy-dispersive X-ray spectroscopy (EDX) cytotoxicity using human gingival fibroblasts and an epithelial cell line. Results The RBC outperformed conventional composite regarding mechanical characteristics (hardness) and monomer eluation, but showed some worrisome results regarding cytotoxicity. Significance The cost benefit is not in favour of RBCs in comparison to conventional composites, as the cytotoxicity was found higher for RBCs.

• Johnsen, Gaute Floer; Dara, Sazan; Asjad, Sameenah; Sunde, Pia Titterud & Haugen, Håvard Jostein (2017). Anatomic Comparison of Contralateral Premolars. Journal of Endodontics.  ISSN 0099-2399.  43(6), s 956- 963 . doi: 10.1016/j.joen.2017.01.012 Vis sammendrag

  Introduction The comparative anatomy of contralateral premolars has not been previously studied. The purpose of this micro–computed tomography investigation was to qualitatively and quantitatively assess and compare the morphology of contralateral premolars in terms of length, canal width, dentinal thicknesses, accessory canals, root canal configurations, isthmi, C-shapes, root canal orifices, and apical foramina. The null hypothesis (H0) is that contralateral premolars are more morphologically similar than randomly assigned pairs for simple morphometric measurements (lengths, canal widths, and dentinal thickness). Methods Forty-one intact premolar pairs (n = 82) extracted from 28 patients were scanned with micro–computed tomography and reconstructed. Quantitative comparative assessment of measurements was performed by pairwise statistical analysis of contralateral and random pairs with Student t test and one-sample t test. All measured parameters (lengths, widths, and thicknesses) were normalized by Z score so that they could all be compared on a common scale. A correlation study was also performed. Canal configurations and isthmi were classified according to preexisting classification schemes. The number and location of accessory canals and apical foramina were registered and compared. Results/Conclusions Contralateral premolar pairs demonstrated a high degree of similarity in terms of the linear measurements (lengths, widths, and thicknesses). The apical portion (foramina, C-shapes, and accessory canals) did not demonstrate bilateral symmetry. The comprehensive statistical analysis of the normalized parameters by Z score showed no statistically significant differences between the contralateral premolar pairs. The null hypothesis (H0) was accepted.

• Johnsen, Gaute Floer; Thieu, Minh Khai Le; Hussain, Badra; Pamula, Elzbieta; Reseland, Janne Elin; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2017). Own brand label restorative materials - A false bargain?. Journal of Dentistry.  ISSN 0300-5712.  56, s 84- 98 . doi: 10.1016/j.jdent.2016.11.004 Vis sammendrag

  Objectives This study aims at evaluating and comparing mechanical, chemical, and cytotoxicological parameters of a commercial brand name composite material against two ‘own brand label' (OBL) composites. Methods Parameters included depth of cure, flexural strength, degree of conversion, polymerization shrinkage, filler particle morphology and elemental analyses, Vickers hardness, surface roughness parameters after abrasion, monomer elution, and cytotoxicity. Results The conventional composite outperformed the OBLS in terms of depth of cure (p < 0.001), degree of cure at the first and last time intervals (p < 0.001), hardness (p < 0.001), and post-abrasion roughness (p < 0.05). The polymerization volumetric shrinkage ranged from 2.86% to 4.13%, with the highest shrinkage seen among the OBLs. Both Monomer elution from the OBLs was statistically significantly higher (p<0.001). Statistically significantly higher cytotoxicity combined with altered morphology and loss of confluence was detected in the cells exposed to extracts from the OBLs. Conclusions The OBLs were in general outdone by the conventional composite. Clinical Significance: OBLs restorative materials have become pervasive in the dental market. Manufacturers often promise equal or better characteristics than existing brand-name composites, but at a lower price. Dentists are highly recommended to reconsider utilization of OBLs lacking sound scientific scrutiny, and our findings underscore this recommendation

• Rumian, Lucja; Tiainen, Hanna; Cibor, Urszula; Krok-Borkowicz, Małgorzata; Brzychczy-Włoch, Monika; Haugen, Håvard Jostein & Pamuła, Elżbieta (2017). Ceramic scaffolds with immobilized vancomycin-loaded poly(lactide-co-glycolide) microparticles for bone defects treatment. Materials letters (General ed.).  ISSN 0167-577X.  190, s 67- 70 . doi: 10.1016/j.matlet.2016.12.113
• Sike, Adam; Wengenroth, Jonas; Upite, Jolanta; Brüning, Thomas; Eiriz Delgado, Iván; Santha, Petra; Biverstål, Henrik; Jansone, Baiba; Haugen, Håvard Jostein; Krohn, Markus & Pahnke, Jens (2017). Improved method for cannula fixation for long-term intracerebral brain infusion. Journal of Neuroscience Methods.  ISSN 0165-0270.  290, s 145- 150 . doi: 10.1016/j.jneumeth.2017.07.026
• Crica, Livia Elena; Wengenroth, Jonas; Tiainen, Hanna; Ionita, Mariana & Haugen, Håvard Jostein (2016). Enhanced X-ray absorption for micro-CT analysis of low density polymers. Journal of Biomaterials Science. Polymer Edition.  ISSN 0920-5063.  27(9), s 805- 823 . doi: 10.1080/09205063.2016.1152856 Vis sammendrag

  X-ray microtomography (micro-CT), one of the most resourceful instruments for high resolution 3D analysis, can provide qualitative and quantitative accurate structural and compositional information for a broad range of materials. Yet its contribution to the field of biopolymeric materials science is often limited by low imaging contrast due to scarce X-ray attenuation features, particularly for sponges and foam-like structures. This limitation can be overcome to some extent by adjusting the working parameters of micro-CT equipment. However, such approach also facilitates noise and artefacts, and solving the signal-to-noise trade-off has been always problematic. Searching for alternatives turns one’s attention towards the improvement of X-ray attenuation features. While several studies report the use of contrast agents for biological materials, studies to integrate multiple micro-CT approaches for biopolymers were not conducted so far. This method paper is thus aimed to serve as a platform for micro-CT analysis of low X-ray absorptive polymers. Here, several contrast enhancing artifices were developed and trialled on gelatin and poly(vinyl alcohol) biopolymer composites (GP). Accordingly, GP were modified with iodine, barium, silver-based chemicals and hexa(methyl disilazane) by two different methods, i.e. addition of high atomic number chemicals during materials synthesis and post-synthesis staining, respectively. Consequently, cross-sectional scanning electron microscopy was emerged as complementary characterization, aimed to confirm the reproducibility of samples morphological features. The most versatile methods were barium chloride additive incorporation and iodine staining coupled with hexa(methyl disilazane) chemical drying. Both methods significantly improved the X-ray absorbance of our polymeric samples, providing better contrast of micro-CT tomograms.

• Geissler, Sebastian; Tiainen, Hanna & Haugen, Håvard Jostein (2016). Effect of cathodic polarization on coating doxycycline on titanium surfaces. Materials Science and Engineering C: Materials for Biological Applications.  ISSN 0928-4931.  63, s 359- 366 . doi: 10.1016/j.msec.2016.03.012
• Ionita, Mariana; Crica, Livia e; Vasile, Eugenia; Dinescu, Sorina; Pandele, Madalina Andreea; Costache, Marieta; Haugen, Håvard Jostein & Iovu, Horia (2016). Effect of carboxylic acid functionalized graphene on physical-chemical and biological performances of polysulfone porous films. Polymer.  ISSN 0032-3861.  92, s 1- 12 . doi: 10.1016/j.polymer.2016.03.040 Vis sammendrag

  This study highlights the preparation and characterization of new polysulfone/carboxylic acid functionalized graphene (PSF/G-COOH) porous composite films. Materials structure, morphology, topography, hydrophilic-hydrophobic character, as well as thermal, mechanical and biological behavior were thoroughly evaluated. Raman spectrometry, X-ray diffraction and transmission electron microscopy evidenced the formation of homogenous configurations, with well-dispersed G-COOH layers within the PSF matrix. Both film sides were found to develop larger pores in the presence of G-COOH, whereas changes of selective layer thickness and macrovoids shape were also observed. Profilometry emphasized a smoothing effect imposed by G-COOH on both surfaces, ∼50% reduction of surface roughness was computed for 2 wt.% G-COOH. No significant vary was noticed for water contact angle, whereas biocomposites thermal and mechanical stability were found to be positively related to G-COOH concentrations. Biocompatibility and cell cytoskeleton assessments revealed good biocompatibility and emphasized cells affinity for G-COOH rich areas.

• Johnsen, Gaute Floer; Sundnes, Joakim; Wengenroth, Jonas & Haugen, Håvard Jostein (2016). Methodology for Morphometric Analysis of Modern Human contralateral Premolars. Journal of computer assisted tomography.  ISSN 0363-8715.  40(4), s 617- 625 . doi: 10.1097/RCT.0000000000000417
• Müller, Benjamin; Haugen, Håvard Jostein; Nilsen, Ola & Tiainen, Hanna (2016). Atomic layer deposited TiO2 protects porous ceramic foams from grain boundary corrosion. Corrosion Science.  ISSN 0010-938X.  106, s 35- 42 . doi: 10.1016/j.corsci.2016.01.023 Vis sammendrag

  Intergranular corrosion causes a significant loss of compressive strength in highly porous TiO2 foams. In this study, the resistance of conformal atomic layer deposited (ALD) coatings against intergranular corrosion has been investigated. ALD coated TiO2 foams maintained 107% ± 20% and 94% ± 10% of their initial compressive strength for films deposited at 150 °C and 250 °C, respectively. After an immersion period of 28 days in 1 mM HCl, amorphous films showed greater potential in corrosion protection of polycrystalline TiO2 foams. However, anatase coatings with sufficient protection may be more beneficial for cell-material interactions.

• Müller, Benjamin; Haugen, Håvard Jostein; Simonsen, Siri Lene & Tiainen, Hanna (2016). Grain boundary corrosion of highly porous ceramic TiO&lt;sub&gt;2&lt;/sub&gt; foams is reduced by annealing and quenching. Journal of the European Ceramic Society.  ISSN 0955-2219.  36(1), s 179- 188 . doi: 10.1016/j.jeurceramsoc.2015.09.014
• Rumian, Lucja; Tiainen, Hanna; Cibor, Urszula; Krok, Malgorzata; Brzychczy-Wloch, Monika; Haugen, Håvard Jostein & Pamula, Elzbieta (2016). Ceramic scaffolds enriched with gentamicin loaded poly(lactide-co-glycolide) microparticles for prevention and treatment of bone tissue infections. Materials Science and Engineering C: Materials for Biological Applications.  ISSN 0928-4931. . doi: 10.1016/j.msec.2016.07.065
• Verket, Anders; Müller, Benjamin; Wohlfahrt, Johan Caspar; Lyngstadaas, Ståle Petter; Ellingsen, Jan Eirik; Haugen, Håvard Jostein & Tiainen, Hanna (2016). TiO2 scaffolds in peri-implant dehiscence defects: an experimental pilot study. Clinical Oral Implants Research.  ISSN 0905-7161.  27(10), s 1200- 1206 . doi: 10.1111/clr.12725
• Wiedmer, David; Sagstuen, Einar; Welch, Ken; Haugen, Håvard Jostein & Tiainen, Hanna (2016). Oxidative power of aqueous non-irradiated TiO2-H2O2 suspensions: Methylene blue degradation and the role of reactive oxygen species. Applied Catalysis B: Environmental.  ISSN 0926-3373.  198, s 9- 15 . doi: 10.1016/j.apcatb.2016.05.036 Vis sammendrag

  In the present study, the degradation of methylene blue in non-irradiated TiO2-H2O2 suspensions was investigated. Five commercially available catalysts were characterised (BET surface area, zeta potential, hydrodynamic diameter) and their oxidative power was assessed by means of the degradation of methylene blue. A subsequent EPR study was made to verify and identify potential oxidative radicals. The results showed that all suspensions could degrade methylene blue significantly stronger compared to hydrogen peroxide alone. A broad variation between the different catalysts in their capability to adsorb dye molecules was found which was essential for decomposition of methylene blue in darkness. The highest degradation rate of all samples was found for Degussa P25 at neutral pH. EPR studies of this sample verified the presence of oxygen centred radicals namely hydroxyl (radical dotOH) and superoxide radicals (O2−radical dot/radical dotOOH). Non-irradiated TiO2-H2O2 systems show great potential not only in dye removal applications but also in the field of disinfection where low concentrations of hydrogen peroxide are required and irradiation may not be feasible.

• Wiig, Elisabeth; Reseland, Janne Elin; Østbye, Kjartan; Haugen, Håvard Jostein & Vøllestad, Leif Asbjørn (2016). Variation in Lateral Plate Quality in Threespine Stickleback from Fresh, Brackish and Marine Water: A Micro-Computed Tomography Study. PLoS ONE.  ISSN 1932-6203.  11(10) . doi: 10.1371/journal.pone.0164578
• Bertoldi, Serena; Fare, Silvia; Haugen, Håvard Jostein & Tanzi, Maria Cristina (2015). Exploiting novel sterilization techniques for porous polyurethane scaffolds. Journal of materials science. Materials in medicine.  ISSN 0957-4530.  26(5), s 5509 . doi: 10.1007/s10856-015-5509-0 Vis sammendrag

  Porous polyurethane (PU) structures raise increasing interest as scaffolds in tissue engineering applications. Understanding the effects of sterilization on their properties is mandatory to assess their potential use in the clinical practice. The aim of this work is the evaluation of the effects of two innovative sterilization techniques (i.e. plasma, Sterrad system, and ozone) on the morphological, chemico-physical and mechanical properties of a PU foam synthesized by gas foaming, using water as expanding agent. In addition, possible toxic effects of the sterilization were evaluated by in vitro cytotoxicity tests. Plasma sterilization did not affect the morphological and mechanical properties of the PU foam, but caused at some extent degradative phenomena, as detected by infrared spectroscopy. Ozone sterilization had a major effect on foam morphology, causing the formation of new small pores, and stronger degradation and oxidation on the structure of the material. These modifications affected the mechanical properties of the sterilized PU foam too. Even though, no cytotoxic effects were observed after both plasma and ozone sterilization, as confirmed by the good values of cell viability assessed by Alamar Blue assay. The results here obtained can help in understanding the effects of sterilization procedures on porous polymeric scaffolds, and how the scaffold morphology, in particular porosity, can influence the effects of sterilization, and viceversa.

• Ionita, Mariana; Crica, Livia E; Tiainen, Hanna; Haugen, Håvard Jostein; Vasile, Eugenia; Dinescu, Sorina; Costache, Marieta & Iovu, Horia (2015). Gelatin-poly(vinyl alcohol) porous biocomposites reinforced with graphene oxide as biomaterials. Journal of materials chemistry. B.  ISSN 2050-750X.  4(2), s 282- 291 . doi: 10.1039/c5tb02132d
• Müller, Benjamin; Reseland, Janne Elin; Haugen, Håvard Jostein & Tiainen, Hanna (2015). Cell growth on pore-graded biomimetic TiO2 bone scaffolds. Journal of Biomaterials Applications.  ISSN 0885-3282.  29(9), s 1284- 1295 . doi: 10.1177/0885328214559859
• Pullisaar, Helen; Verket, Anders; Szoke, Krisztina; Tiainen, Hanna; Haugen, Håvard Jostein; Brinchmann, Jan E.; Reseland, Janne Elin & Østrup, Esben (2015). Alginate hydrogel enriched with enamel matrix derivative to target osteogenic cell differentiation in TiO2 scaffolds. Journal of Tissue Engineering.  ISSN 2041-7314.  6 . doi: 10.1177/2041731415575870 Fulltekst i vitenarkiv.
• Rumian, Lucja; Reczynska, Katarzyna; Wrona, Małgorzata; Tiainen, Hanna; Haugen, Håvard Jostein & Pamula, Elzbieta (2015). The influence of sintering conditions on microstructure and mechanical properties of titanium dioxide scaffolds for the treatment of bone tissue defects. Acta of Bioengineering and Biomechanics.  ISSN 1509-409X.  17(1), s 3- 9 . doi: 10.5277/ABB-00129-2014-02 Vis sammendrag

  In this study the attempts to improve mechanical properties of highly-porous titanium dioxide scaffolds produced by polymer sponge replication method were investigated. Particularly the effect of two-step sintering at different conditions on microstructure (studied by microcomputed tomography and scanning electron microscopy) and mechanical properties (compression test) of the scaffolds were analysed. Our experiments showed that the most appropriate conditions of manufacturing were when the scaffolds were heat-treated at 1500 oC for 1 h followed by sintering at 1200 oC for 20 h. Such scaffolds exhibited the highest compressive strength which was correlated with the highest linear density and the lowest size of grains. Moreover, grain size distribution was narrower with predominating fraction of fine grains 10-20 µm in size. Smaller grains and higher linear density suggested that in this case densification process prevailed undesirable process of grain coarsening, what finally resulted in improved mechanical properties of the scaffolds.

• Xing, Rui; Lyngstadaas, Ståle Petter; Ellingsen, Jan Eirik; Taxt-Lamolle, Sebastien Francis Michel & Haugen, Håvard Jostein (2015). The influence of surface nanoroughness, texture and chemistry of TiZr implant abutment on oral biofilm accumulation. Clinical Oral Implants Research.  ISSN 0905-7161.  26(6), s 649- 656 . doi: 10.1111/clr.12354 Vis sammendrag

  Objectives The aim of the study was to examine surface nanoroughness, texture and chemistry of dental implant abutment and to investigate how these parameters influence oral biofilm formation in healthy subjects. Materials and methods Eight different nanorough TiZr surfaces were produced by polishing, machining, cathodic polarization and acid etching. Surface topography was examined using field emission scanning electron microscope and a blue light laser profilometer. Surface chemistry was analyzed by secondary ion mass spectrometry and X-ray photoelectron spectroscopy. Surface hydrophilicity was tested by measuring contact angle on the surfaces. A human in vivo study using a splint model was employed to evaluate oral biofilm accumulation on these surfaces. Results Different surface textures (flat, grooved and irregular) were created with nanoroughness from 29 to 214 nm. Some test surfaces were incorporated with hydrogen by cathodic polarization and/or acid etching with HCl/H2SO4. Nanoroughness (Sa) positively correlated with microbial adhesion. Biofilm accumulation was less pronounced on flat and grooved than on irregular surfaces. No significant association between hydrogen content or hydrophilicity of the surface and biofilm accumulation was observed. Conclusions Nanoroughness (< 214 nm) and surface texture influence oral biofilm accumulation independent of surface chemistry and hydrophilicity. Surface hydrogen, which has previously been shown to promote fibroblast growth, does not affect biofilm formation

• Xing, Rui; Witsø, Ingun Lund; Jugowiec, David; Tiainen, Hanna; Shabestari, Maziar; Lyngstadaas, Ståle Petter; Lönn-Stensrud, Jessica & Haugen, Håvard Jostein (2015). Antibacterial effect of doxycycline-coated dental abutment surfaces. Biomedical Materials.  ISSN 1748-6041.  10(5), s 55003- 55012 . doi: 10.1088/1748-6041/10/5/055003 Vis sammendrag

  Biofilm formation on dental abutment may lead to peri-implant mucositis and subsequent peri-implantitis. These cases are clinically treated with antibiotics such as doxycycline (Doxy). Here we used an electrochemical method of cathodic polarization to coat Doxy onto the outer surface of a dental abutment material. The Doxy-coated surface showed a burst release in phosphate-buffered saline during the first 24 h. However, a significant amount of Doxy remained on the surface for at least 2 weeks especially on a 5 mA–3 h sample with a higher Doxy amount, suggesting both an initial and a long-term bacteriostatic potential of the coated surface. Surface chemistry was analyzed by x-ray photoelectron spectroscopy and secondary ion mass spectrometry. Surface topography was evaluated by field emission scanning electron microscopy and blue-light profilometry. Longer polarization time from 1 h to 5 h and higher current density from 1 to 15 mA cm−2 resulted in a higher amount of Doxy on the surface. The surface was covered by a layer of Doxy less than 100 nm without significant changes in surface topography. The antibacterial property of the Doxy-coated surface was analyzed by biofilm and planktonic growth assays using Staphylococcus epidermidis. Doxy-coated samples reduced both biofilm accumulation and planktonic growth in broth culture, and also inhibited bacterial growth on agar plates. The antibacterial effect was stronger for samples of 5 mA–3 h coated with a higher amount of Doxy compared to that of 1 mA–1 h. Accordingly, an abutment surface coated with Doxy has potential for preventing bacterial colonization when exposed to the oral cavity. Doxy-coating could be a viable way to control peri-implant mucositis and prevent its progression into peri-implantitis.

• Frank, Matthias Johannes; Walter, Martin Sebastian; Rubert, Marina; Thiede, Bernd; Monjo Cabrer, Marta; Reseland, Janne Elin; Haugen, Håvard Jostein & Lyngstadaas, Ståle Petter (2014). Cathodic polarization coats titanium based implant materials with enamel matrix derivate (EMD). Materials.  ISSN 1996-1944.  7(3), s 2210- 2228 . doi: 10.3390/ma7032210 Fulltekst i vitenarkiv. Vis sammendrag

  The idea of a bioactive surface coating that enhances bone healing and bone growth is a strong focus of on-going research for bone implant materials. Enamel matrix derivate (EMD) is well documented to support bone regeneration and activates growth of mesenchymal tissues. Thus, it is a prime candidate for coating of existing implant surfaces. The aim of this study was to show that cathodic polarization can be used for coating commercially available implant surfaces with an immobilized but functional and bio-available surface layer of EMD. After coating, XPS revealed EMD-related bindings on the surface while SIMS showed incorporation of EMD into the surface. The hydride layer of the original surface could be activated for coating in an integrated one-step process that did not require any pre-treatment of the surface. SEM images showed nano-spheres and nano-rods on coated surfaces that were EMD-related. Moreover, the surface roughness remained unchanged after coating, as it was shown by optical profilometry. The mass peaks observed in the matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS) analysis confirmed the integrity of EMD after coating. Assessment of the bioavailability suggested that the modified surfaces were active for osteoblast like MC3M3-E1 cells in showing enhanced Coll-1 gene expression and ALP activity.

• Gomez-Florit, Manuel; Ramis, Joana Maria; Xing, Rui; Taxt-Lamolle, Sebastien Francis Michel; Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter & Monjo Cabrer, Marta (2014). Differential response of human gingival fibroblasts to titanium- and titanium-zirconium-modified surfaces. Journal of Periodontal Research.  ISSN 0022-3484.  49(4), s 425- 436 . doi: 10.1111/jre.12121 Vis sammendrag

  Background and Objective: Gingival fibroblasts are responsible for the constant adaptation, wound healing and regeneration of gingival connective tissue. New titanium-zirconium (TiZr) abutment surfaces have been designed to improve soft tissue integration and reduce implant failure compared with titanium (Ti). The aim of the present study was firstly to characterize a primary human gingival fibroblasts (HGF) model and secondly to evaluate their differential response to Ti and TiZr polished (P), machined (M), and machined + acid-etched (modMA) surfaces, respectively. Material and Methods: HGF were cultured on tissue culture plastic or on the different Ti and TiZr surfaces. Cell morphology was evaluated through confocal and scanning electron microscopy. A wound healing assay was performed to evaluate the capacity of HGF to close a scratch. The expression of genes addressing (a) ECM organization and turnover, (b) inflammation, (c) cell adhesion and structure and (d) wound healing was evaluated by real time RT-PCR. Finally, cells on Ti/TiZr surfaces were immunostained with anti-ITGB3 antibodies to analyze integrin β3 production. Matrix metalloproteinane-1 (MMP1) and inhibitor of metallopeptidases-1 (TIMP1) production were analyzed by enzyme-linked immunosorbent assays. Results: On tissue culture plastic, HGF showed no differences between donors on cell proliferation and on the ability for wound closure; α-smooth muscle actin was overexpressed on scratched monolayers. The differentiation profile showed increased production of extracellular matrix components. Ti and TiZr showed similar biocompatibility with HGF. TiZr increased integrin-β3 mRNA and protein levels, compared with Ti. Cells on TiZr surfaces showed higher MMP1 protein than Ti surfaces, although similar TIMP1 protein production. In this in vitro experiment, P and M surfaces from both Ti and TiZr showed better HGF growth than modMA. Conclusion: Taking into account the better mechanical properties and bioactivity of TiZr compared with Ti, the results of the present study show that TiZr is a potential clinical candidate for soft tissue integration and implant success.

• Gomez-Florit, Manuel; Xing, Rui; Ramis, Joana Maria; Taxt-Lamolle, Sebastien Francis Michel; Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter & Monjo Cabrer, Marta (2014). Human gingival fibroblasts function is stimulated on machined hydrided titanium zirconium dental implants. Journal of Dentistry.  ISSN 0300-5712.  42(1), s 30- 38 . doi: 10.1016/j.jdent.2013.11.003 Vis sammendrag

  Objectives The aim of this study was to evaluate the influence of different titanium zirconium (TiZr) alloy surfaces on primary human gingival fibroblasts (HGF) for improved soft tissue integration of dental implants. Methods TiZr polished, machined and machined+HCl/H2SO4 acid-etched surfaces were modified by cathodic polarization and/or HNO3/HF acid etching. Contact angle of surfaces was measured. The influence of modified TiZr surfaces on HGF was evaluated through the analysis of cell number, morphology, recovery after a wound (wound healing assay) and the expression of several genes, including matrix metalloproteinase-1 (MMP1) and metallopeptidase inhibitor-1 (TIMP1). Results Modification of TiZr surfaces decreased its hydrophilicity. Hydride implementation on TiZr surfaces via cathodic polarization increased TIMP1 expression and decreased MMP1/TIMP1 mRNA ratio. Cathodic polarization of machined surfaces promoted cell attachment. Cells on machined and machined + cathodic polarization surfaces grew aligned to the microgrooves whereas on all polished surfaces they grew randomly. Acid etching of polished and machined surfaces did not improve HGF function. Conclusions Hydride implementation on TiZr machined surfaces may be used as new dental implant material for improved soft tissue integration.

• Gordeladze, Jan Oxholm; Stakkestad, Øystein; Haugen, Sigrid; Reseland, Janne Elin; Syversen, Unni; Johnsen, Gaute Floer; Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter; Møller, Mona & Valtieri, Mauro (2014). Regulatory Loops Consisting of Transcription Factors and MicroRNA Species Determining the Mineralizing Characteristics of Cell Phenotypes - Implications for Bone Engineering and Prevention of Soft Tissue Mineralization, In Daniel Eberli (ed.),  Cells and Biomaterials in Regenerative Medicine.  INTECH.  ISBN 978-953-51-1731-5.  Chapter 3.
• Kopperud, Hilde Beate M.; Johnsen, Gaute Floer; Lamolle, Sebastien Francis; Kleven, Inger Julie Sjøvik; Wellendorf, Hanne & Haugen, Håvard Jostein (2014). Effekt av kort herdetid på kjemiske og mekaniske egenskaper til kompositter. Den norske tannlegeforenings tidende.  ISSN 0029-2303.  124, s 356- 362
• Pham, Thi Ngoc Maria Huong; Landin, Maria Augusta Dos S Silva; Tiainen, Hanna; Reseland, Janne Elin; Ellingsen, Jan Eirik & Haugen, Håvard Jostein (2014). The effect of hydrofluoric acid treatment of titanium and titanium dioxide surface on primary human osteoblasts. Clinical Oral Implants Research.  ISSN 0905-7161.  25(3), s 385- 394 . doi: 10.1111/clr.12150 Vis sammendrag

  Abstract Objective The aim of the study was to investigate solely the effect of fluoride on the surface chemistry of polycrystalline ceramic titanium dioxide (TiO2) and metallic titanium (Ti) and its effect on proliferation and differentiation of primary human osteoblasts (NHO). Materials and methods The NHO cells were exposed to fluoride-modified and unmodified samples for 1, 3, 7, 14 and 21 days. The fluoride effect on the mRNA expression was quantified and measured. The secretion of cytokines and interleukins in the cell culture medium was measured by Luminex, gene expression by RT-PCR, and compared with untreated controls. The effect on cell growth after 1 and 3 days in culture was measured using [3H]-thymidine incorporation. Fluoride release was measured using an ion-selective electrode. The surfaces were examined by X-ray photoelectron spectroscopy and profilometry. Results The fluoride release study detected that fluoride content easily washed off in TiO2 coins when compared with Ti coins. No increase in cell proliferation was found among fluoride-modified TiO2 surfaces compared with controls, except for washed Ti coins with fluoride modification. The cell differentiation with regard to gene expression showed no significant differences in both fluoride-modified and unmodified samples and less effect on protein release for all groups. Conclusions The fluoride from hydrofluoric acid treatment on Ti and TiO2 surfaces gave no specific effect on primary human osteoblast cells. The study indicates that the released fluoride is not the unique factor for the bioactivity of Ti and TiO2 surfaces.

• Pullisaar, Helen; Reseland, Janne Elin; Haugen, Håvard Jostein; Brinchmann, Jan E. & Østrup, Esben (2014). Simvastatin coating of TiO2 scaffold induces osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells. Biochemical and Biophysical Research Communications - BBRC.  ISSN 0006-291X.  447(1), s 139- 144 . doi: 10.1016/j.bbrc.2014.03.133
• Walter, Martin Sebastian; Frank, Matthias Johannes; Rubert, Marina; Monjo, Marta; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2014). Simvastatin-activated implant surface promotes osteoblast differentiation in vitro. Journal of Biomaterials Applications.  ISSN 0885-3282.  28(6), s 897- 908 . doi: 10.1177/0885328213486364 Vis sammendrag

  The bone growth promoting effects of statins suggest that these bioactive molecules can be used to improve the integration of bone-anchored implants. This study aimed at the application of simvastatin with dental implants for use in patients with low bone density. Coin-shaped titanium zirconium samples with grit-blasted and acid-etched surface were coated with simvastatin, using a novel anodic oxidation setup under alkaline conditions. The presence of intact simvastatin attached to the surface was confirmed by infrared spectroscopy. A binding site on the aliphatic O-H group was discovered and the integration of 1H, 18O and 12C in the depth of the surface were observed by secondary ion mass spectroscopy. A simvastatin concentration of about 60 g/cm2 was found in a release study over 72 h. The simvastatincoated surfaces promoted alkaline phosphatase, collagen type I and osteocalcin gene expression of MC3T3-E1 cells. This suggested that the demonstrated coating holds potential for use in patients with compromised bone.

• Walter, Martin Sebastian; Frank, Matthias Johannes; Satué, María; Monjo Cabrer, Marta; Rønold, Hans Jacob; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2014). Bioactive Implant Surface with Electrochemically Bound Doxycycline Promotes Bone Formation Markers In Vitro and In Vivo. Dental Materials.  ISSN 0109-5641.  30(2), s 200- 214 . doi: 10.1016/j.dental.2013.11.006 Vis sammendrag

  Objectives: The objective of this study was to demonstrate a successful binding of Doxy hyclate onto a titanium zirconium alloy surface. Method: The coating was done on titanium zirconium coins in a cathodic polarization setup. The surface binding was analysed by SEM, SIMS, UV-Vis, FTIR and XPS. The in vitro biological response was tested with MC3T3-E1 murine pre-osteoblast cells after 14 days of cultivation and analysed in RT-PCR. A rabbit tibial model was also used to confirm its bioactivity in vivo after 4 and 8 weeks healing by means of microCT. Results: A mean of 141 µg/cm² of Doxy was found firmly attached and undamaged on the surface. Inclusion of Doxy was documented up to a depth of approximately 0.44 µm by tracing the 12C carbon isotope. The bioactivity of the coating was documented by an in vitro study with murine osteoblasts, which showed significantly increased alkaline phosphatase and osteocalcin gene expression levels after 14 days of cell culture along with low cytotoxicity. Doxy coated surfaces showed increased bone formation markers at 8 weeks of healing in a rabbit tibial model. Significance: The present work demonstrates a method of binding the broad spectrum antibiotic doxycycline (Doxy) to an implant surface to improve bone formation and reduce the risk of infection around the implant. We have demonstrated that TiZr implants with electrochemically bound Doxy promote bone formation markers in vitro and in vivo.

• Xing, Rui; Salou, Laëtitia; Taxt-Lamolle, Sebastien Francis Michel; Reseland, Janne Elin; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2014). Surface Hydride on Titanium by Cathodic Polarization Promotes Human Gingival Fibroblast Growth. Journal of Biomedical Materials Research. Part A.  ISSN 1549-3296.  102(5), s 1389- 1398 . doi: 10.1002/jbm.a.34819 Vis sammendrag

  Connective tissue seal to dental abutment is crucial for peri-implant health. Several efforts have previously been made to optimize abutment surfaces, but no consensus has been reached regarding the optimal surface architecture and/or composition for soft tissue seal. Here we report on experiments using cathodic polarization in organic acids to optimize titanium (Ti) surfaces for use as abutments. The three main factors affecting surface topography and chemistry were electrolyte composition, current density and polarization time. Under identical conditions, oxalic acid created rougher surfaces than tartaric acid and acetic acid, and acetic acid produced more surface hydride. Surface hydride amount was suggested to first increase and then decrease with current density from 1 to 15 mA/cm2. The complexity of the surface topography and hydride production both increased with polarization time. Proliferation rate of human gingival fibroblasts (HGF) was positively correlated with surface hydride content, suggesting the positive effect of surface hydride to connective tissue growth around dental abutment. Changes in surface topography and hydrophilicity did not significantly influence HGF growth.

• Tiainen, Hanna; Wiedmer, David & Haugen, Håvard Jostein (2013). Processing of highly porous TiO2 bone scaffolds with improved compressive strength. Journal of the European Ceramic Society.  ISSN 0955-2219.  33(1), s 15- 24 . doi: 10.1016/j.jeurceramsoc.2012.08.016 Vis sammendrag

  In the present study, the effect of sintering time and recoating procedures on the pore architectural parameters and compressive strength of highly porous ceramic TiO2 foams were investigated. Long sintering times (>5 h) at 1500 °C led to an inward collapse of one wall of the triangular voids typically found in the strut interior of foams prepared using the replication method. This strut folding led to increased compressive strength, while the pore architectural features were not significantly affected. Furthermore, majority of the internal porosity of the foam struts was partially eliminated and became accessible for infiltration with TiO2 slurry. Recoating procedures were found to markedly reduce the flaw size and number in the TiO2 foam struts, which led to significant strengthening of the ceramic structure (0.7 → 3.4 MPa) by improved structural uniformity and slightly increased strut diameter.

• Frank, Matthias Johannes; Walter, Martin Sebastian; Bucko, Miroslaw M.; Pamula, Elzbieta; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2013). Polarization of modified titanium and titanium-zirconium creates nano-structures while hydride formation is modulated. Applied Surface Science.  ISSN 0169-4332.  282, s 7- 16 . doi: 10.1016/j.apsusc.2013.04.059 Vis sammendrag

  The majority of titanium based bone-level dental implants available on the market today feature a sand-blasted and acid-etched (SBAE) surface that contains comparably high hydrogen levels. Cathodic polarization of titanium in acidic solutions is known to further increase titanium hydride on the surface. The aim of this study was to explore the effect of cathodic reduction ontitanium (Ti) and titanium-zirconium (TiZr)with a SBAE surface in order to investigate the potential of such a process for further improving surfaces for bone anchored dental implants. Samples of both materials were cathodically polarized in acidic solution at different current densities and for different process times. Chemical analysis of the hydrogen levels by SIMS showed that cathodic reduction re-arranged the hydride already present on the surfaces from the etching process but could not significantly increase hydride levels.The hydrogen layer created by the preceding hot acid etching appeared to modulate further hydride creation. Analysis of the surface topography by SEM showed changes to the nano-topography of both materials after polarization. TiZr showed homogeneously distributed nano-spheres as they were already observed for TiZr SBAE at increased size of 80 nm–100 nm on the whole surface.By contrast, polarization of Ti created nano-nodules and nano-spheresof 150 nm–200 nm on the surface.These spheres were interconnected to form flower-like structures along the ridges and peaks of the surface. Moreover the flanks were covered by a rippled structure of isotropically distributed small-diameter (10 nm–20 nm) nano-nodules.

• Frank, Matthias Johannes; Walter, Martin Sebastian; Tiainen, Hanna; Rubert, Marina; Monjo, Marta; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2013). Coating of metal implant materials with strontium. Journal of materials science. Materials in medicine.  ISSN 0957-4530.  24(11), s 2537- 2548 . doi: 10.1007/s10856-013-5007-1
• Haugen, Håvard Jostein; Monjo Cabrer, Marta; Rubert, Marina; Verket, Anders; Lyngstadaas, Ståle Petter; Ellingsen, Jan Eirik; Rønold, Hans Jacob & Wohlfahrt, Johan Caspar (2013). Porous Ceramic Titanium Dioxide Scaffolds Promote Bone Formation in Rabbit Peri-Implant Cortical Defect Model. Acta Biomaterialia.  ISSN 1742-7061.  9(2), s 5390- 5399 . doi: 10.1016/j.actbio.2012.09.009 Vis sammendrag

  Titanium oxide (TiO2) scaffolds have previously been reported to exhibit very low mechanical strength. However, we have been able to produce a scaffold that features a high interconnectivity, a porosity of 91% and a compressive strength above 1.2 MPa. This study analysed the in vivo performance of the porous TiO2 scaffolds in a peri-implant cortical defect model in the rabbit. After 8 weeks of healing, morphological microCT analyses of the defects treated with the TiO2 scaffolds had significantly higher bone volume, bone surface and bone surface to volume ratio when compared to sham, both in the cortical and bone marrow compartment. No adverse effects, i.e. tissue necrosis or inflammation as measured by LDH activity and real-time RT-PCR analysis were observed. Moreover, the scaffold did not hinder bone growth onto the adjacent cortical titanium implant. Histology clearly demonstrated new bone formation in the cortical sections of the defects and presence of newly formed bone in close proximity to the scaffold surface and the surface of the adjacent Ti implant. Bone to material contact between the newly formed bone and the scaffold was observed in the histological sections. Islets of new bone were also present in the marrow compartment albeit in scarce amounts. In conclusion, the present investigation demonstrates that TiO2 scaffolds osseointegrate well and is a suitable scaffold for peri-implant bone healing and growth. --------------------------------------------------------------------------------

• Henderson, Elisabet; Schneider, Sigurd; Petersen, Fernanda Cristina; Haugen, Håvard Jostein; Wohlfahrt, Johan Caspar; Ekstrand, Karl & Ekfeldt, Anders (2013). Chemical debridement of contaminated titanium surfaces: An in vitro study. Acta Odontologica Scandinavica.  ISSN 0001-6357.  71(3-4), s 957- 964 . doi: 10.3109/00016357.2012.734423 Vis sammendrag

  Abstract Objective. To compare the efficacy of different chemical solutions when used for chemical debridement of biofilm contaminated titanium surfaces in an in-vitro experimental study. Materials and methods. Commercially pure titanium discs with a diameter of 6.2 mm and height of 2 mm, mirror-polished with a measured surface amplitude value S(A) = 0.037 μm ± 0.009 were used as test-surfaces. A biofilm was simulated with multi-layers of Staphylococcus epidermidis ATCC359844 covering the entire titanium surface. The chemical agents tested were: 3% H(2)O(2), 0.2% Chlorhexidine, 24% EDTA-gel, 3% H(2)O(2) mixed with 1.6 g/L TiO(2) and sterile saline solution. The decontamination effect was evaluated by optical density analysis using spectrophotometry and with scanning electron microscopy (SEM) images of the remaining biofilm. Results. The suspensions of 3% H(2)O(2) and 1.6 g/L TiO(2) or 3% H(2)O(2) alone were the most effective in removing S. epidermidis biofilms (p < 0.05), whereas 0.2% chlorhexidine or 24% EDTA gel had no significant effects. SEM images of the remaining biofilms supported the quantitative results indicating the higher efficacy of 3% H(2)O(2) and 1.6 g/L TiO(2) or 3% H(2)O(2) alone. It also revealed that EDTA, despite a non-significant effect on reducing the amount of established biofilms, was able to alter the biofilm architecture, as demonstrated by increased interspaced regions. Conclusions. In this in vitro study the decontamination potential of a suspension of 3% H(2)O(2) and 1.6 g/L TiO(2) or 3% H(2)O(2) alone were encouraging. Whether such procedures would have a similar effect in vivo remains to be determined.

• Kopperud, Hilde Beate M.; Johnsen, Gaute Floer; Lamolle, Sebastien Francis; Kleven, Inger Julie Sjøvik; Wellendorf, Hanne & Haugen, Håvard Jostein (2013). Effect of short LED lamp exposure on wear resistance, residual monomer and degree of conversion for Filtek Z250 and Tetric EvoCeram composites. Dental Materials.  ISSN 0109-5641.  29(8), s 824- 834 . doi: 10.1016/j.dental.2013.04.022 Vis sammendrag

  Objectives. The latest LED dental curing devices claim sufficient curing of restorative materials with short curing times. This study evaluates mechanical and chemical properties asa function of curing time of two commercial composite filling materials cured with threedifferent LED lamps. Methods. The composites were Filtek Z250 (3M ESPE) and Tetric EvoCeram (Ivoclar Vivadent)and the LED curing devices were bluephase 16i (Ivoclar Vivadent), L.E.Demetron II (Kerr) andMini L.E.D. (Satelec). Control samples were cured with a QTH-lamp (VCL 400, Kerr). The wearresistance after simulated tooth brushing, degree of conversion, curing depth, and amountsof residual monomers were measured after different curing times. Results. The results of this study show that short curing time with high-intensity LEDs mayinfluence the bulk properties of the materials, resulting in lower curing depth and increasedresidual monomer content. The measured surface properties of the materials, degree ofconversion and wear resistance, were not affected by short curing times to the same extent. Significance. This study demonstrates that reduced exposure time with high intensity LEDscan result in composite restorations with inferior curing depth and increased leachingof monomers. Dentists are recommended to use sufficient curing times even with highintensity LEDs to ensure adequate curing and minimize the risk of monomer leaching.

• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Reseland, Janne Elin & Østrup, Esben (2013). Enhanced in vitro osteoblast differentiation on TiO2 scaffold coated with alginate hydrogel containing simvastatin. Journal of Tissue Engineering.  ISSN 2041-7314.  4, s 1- 13 . doi: 10.1177/2041731413515670 Fulltekst i vitenarkiv. Vis sammendrag

  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.

• Rubert, Marina; Pullisaar, Helen; Gomez-Florit, Manuel; Ramis, Joana Maria; Tiainen, Hanna; Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter & Monjo Cabrer, Marta (2013). Effect of TiO2 scaffolds coated with alginate hydrogel containing a proline-rich peptide on osteoblast growth and differentiation in vitro. Journal of Biomedical Materials Research. Part A.  ISSN 1549-3296.  101A(6), s 1768- 1777 . doi: 10.1002/jbm.a.34458 Vis sammendrag

  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 48h 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 SEM 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.

• Sanchez, Luis; Taxt-Lamolle, Sebastien Francis Michel; Hole, Eli Olaug; Krivokapic, Andre; Sagstuen, Einar & Haugen, Håvard Jostein (2013). TiO2 suspension exposed to H2O2 in ambient light or darkness: Degradation of methylene blue and EPR evidence for radical oxygen species. Applied Catalysis B: Environmental.  ISSN 0926-3373.  142-143, s 662- 667 . doi: 10.1016/j.apcatb.2013.05.017
• Walter, Martin Sebastian; Frank, Matthias Johannes; Sunding, Martin Fleissner; Gomez-Florit, Manuel; Monjo Cabrer, Marta; Bucko, Miroslaw M.; Pamula, Elzbieta; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2013). Increased reactivity and in vitro cell response of titanium based implant surfaces after anodic oxidation. Journal of materials science. Materials in medicine.  ISSN 0957-4530.  24(12), s 2761- 2773 . doi: 10.1007/s10856-013-5020-4 Vis sammendrag

  In the quest for improved bone growth and attachment around dental implants, chemical surface modifications are one possibility for future developments. The biological properties of titanium based materials can be further enhanced with methods like anodic polarization to produce an active rather than a passive titanium oxide surface. Here we investigate the formation of hydroxide groups on sand blasted and acid etched titanium and titanium–zirconium alloy surfaces after anodic polarization in an alkaline solution. X-ray photoelectron spectroscopy shows that the activated surfaces had increased reactivity. Furthermore the activated surfaces show up to threefold increase in OH− concentration in comparison to the original surface. The surface parameters Sa, Sku, Sdr and Ssk were more closely correlated to time and current density for titanium than for titanium–zirconium. Studies with MC3T3-E1 osteoblastic cells showed that OH− activated surfaces increased mRNA levels of osteocalcin and collagen-I.

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• Gordeladze, Jan Oxholm; Landin, Maria Augusta Dos S Silva; Johnsen, Gaute Floer; Haugen, Håvard Jostein & Osmundsen, Harald (2017). Vitamin K2 and its Impact on Tooth Epigenetics. INTECH.  ISBN 978-953-51-3020-8.  27 s. Vis sammendrag

  The impact of nutritional signals plays an important role in systemic-based «models» of dental caries. Present hypotheses now focus both on the oral environment and other organs, like the nervous system and brain. The tooth is subjected to shear forces, nourishing and cleansing, and its present “support system” (the hypothalamus/parotid axis) relays endocrine signaling to the parotid gland. Sugar consumption enhances hypothalamic oxidative stress (ROS), reversing dentinal fluid flow, thus creating an enhanced vulnerability to the oral bacterial flora. The acid, produced by the oral bacterial flora, then leads to erosion of the dentine, and an irreversible loss of dental enamel layers. This attack brings about inflammatory responses, yielding metalloproteinase-based “dissolution”. However, vitamin K2 (i.e. MK-4/MK-7) may come to the rescue with its antioxidant property, locally (mouth cavity) or systemically (via the brain), thus sustaining/preserving hormone-induced dentinal fluid flow (encompassing oxidative stress) and boosting/magnifying bodily inflammatory responses. However, sugars may also reduce the tooth’s natural defences through endocrine signaling, thus enhancing acid-supported enamel dentine erosion. Vitamin K2 sustains and improves the salivary buffering capacity via its impact on the secretion/flow of calcium and inorganic phosphates. Interestingly, primitive cultures’ diets (low-sugar and high-K2 diets) preserve dental health.

• Haugen, Håvard Jostein & Bertoldi, Serena (2017). 3D porous structures: porosity and other relevant morphological parameters. Woodhead Publishing Limited.  ISBN 9780081007433.  500 s. Vis sammendrag

  Three-dimensional (3D) porous structures find applications in the biomedical field mainly as scaffolds for tissue engineering and regenerative medicine, as for most tissues (eg, bonetissue, bloodvessel, muscletissue) aporoussupportguidinggrowingtissueiscrucial. Their characterization appears to be fundamental, as the architectural parameters, porosity in particular, but also pore size and interconnectivity [1, 2], strongly affect the mechanical and biological performance of the 3D structures [2, 3], and thus their functionality. Effective techniques, able to provide information on scaffold morphological properties, are required at the initial stages of research and development, so to design scaffolds with the optimal properties for the specific application. In addition, since the biological performance of the scaffolds should be evaluated with respect to their ability during time to favor cell adhesion, proliferation, and extracellular matrix production, an analytical technique capable of monitoring the evolving steps of a cell/tissuebiomaterial interaction experiment, both in vitro and in vivo, can be very useful. The need for measurements and standard rules to be applied for scaffold characterization is well identified by scientists and regulators [4], and the debate about that is vivid. Among the morphological parameters to be analyzed (Table 2.1), porosity is the most often quoted [5], as it would influence scaffold mechanical properties and scaffold-cell interactions.

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• Gomez-Florit, Manuel; Reseland, Janne Elin & Haugen, Håvard Jostein (2017). Synthetic intrinsically-disordered-peptides for bone tissue engineering. Vis sammendrag

  DISCUSSION & CONCLUSIONS: Results show that synthetic IDPs are able to influence hOBs biomineralization. The earlier upregulation of osteogenic markers together with the decreased wound area induced by P2 indicate that it has potential to induce bone regeneration. Bone related proteins, cytokines and chemokines released to culture media are already being analysed to confirm these results. IDPs might be a reliable option to develop new biomaterials and tissue engineering strategies

• Haugen, Håvard Jostein; Johnsen, Gaute Floer; Reseland, Janne Elin; Hussain, Badra & Thieu, Minh Khai Le (2017). Can CAD/CAM Resin Blocks be Considered as a Substitute to Conventional Resins?.
• Schneider, Kenneth; Haugen, Håvard Jostein & Linke, Dirk (2017). Assay Development: Adhesin Interaction with Implant Materials.
• Schneider, Kenneth; Saragliadis, Athanasios; Haugen, Håvard Jostein & Linke, Dirk (2016). Aggregatibacter Adhesins and their interaction with implant materials.
• Tiainen, Hanna; Müller, Benjamin; Campos, Lluis; Ramis, Joana Maria; Nilsen, Ola & Haugen, Håvard Jostein (2016). Atomic layer deposited TiO2 protects highly porous ceramic bone scaffolds from grain boundary corrosion.
• Tiainen, Hanna; Müller, Benjamin; Campos, Lluis; Ramis, Joana Maria; Nilsen, Ola & Haugen, Håvard Jostein (2016). Atomic layer deposited titanium dioxide layer protects highly porous ceramic foams from grain boundary corrosion.
• Wiedmer, David; Tiainen, Hanna; Lönn-Stensrud, Jessica; Petersen, Fernanda Cristina & Haugen, Håvard Jostein (2016). TiO2-H2O2 as decontamination agent - an in vitro study.
• Wiedmer, David; Tiainen, Hanna; Petersen, Fernanda Cristina & Haugen, Håvard Jostein (2016). H2O2-TiO2 as potential treatment for peri-implantitis – an in vitro study.
• Chahal, Aman Singh; Schweikle, Manuel; Tiainen, Hanna; Koldsland, Odd Carsten; Reseland, Janne Elin & Haugen, Håvard Jostein (2015). Cell-responsive Biomimetic Extracellular Matrix Material for Bone and Dental Pulp Tissue Regeneration.
• Gandolfi, Maria G; siboni, F; Haugen, Håvard Jostein & Prati, Carli (2015). Chemical–physical properties of innovative polysiloxane–guttapercha calcium silicate-containing systems. Dental Materials.  ISSN 0109-5641.  31(1), s 44- 45 . doi: 10.1016/j.dental.2015.08.099
• Geissler, Sebastian; Tiainen, Hanna & Haugen, Håvard Jostein (2015). Electrochemical attachment of doxycycline to titanium surfaces.
• Geissler, Sebastian; Tiainen, Hanna & Haugen, Håvard Jostein (2015). Electrochemical immobilization of doxycycline on titanium surfaces.
• Geissler, Sebastian; Tiainen, Hanna; Lund, Reidar & Haugen, Håvard Jostein (2015). pH triggered aggregation of an intrinsically disordered proline-rich peptide.
• Janson, Oscar; Unosson, Erik; Wiedmer, David; Haugen, Håvard Jostein; Engqvist, Håkan & Welch, Ken (2015). Aktivering av TiO2 nanopartiklar för desinfektion av tandimplantat.
• Johnsen, Gaute Floer; Wengenroth, Jonas; Sundnes, Joakim & Haugen, Håvard Jostein (2015). Morphometric Micro-CT Comparative Analyses of Contralateral Premolar Pulp Space.
• Longela, Simon Makusudi; Haugen, Håvard Jostein; Hartvig, Rune & Tiainen, Hanna (2015). Biomolecular coating of Nickel-titanium Shape memory metals.
• Longela, Simon Makusudi; Haugen, Håvard Jostein & Tiainen, Hanna (2015). Biomolecular coating of nickel-titanium memory shape metals.
• Longela, Simon Makusudi; Haugen, Håvard Jostein; Tiainen, Hanna & Hartvig, Rune (2015). Surface treatment of pseudoelastic nickel-titanium.
• Longela, Simon Makusudi; Haugen, Håvard Jostein; Tiainen, Hanna; Lyngstadaas, Ståle Petter & Reseland, Janne Elin (2015). Biomolecular coating of nickel-titanium memory shape metals. European Cells and Materials.  ISSN 1473-2262.  29, s 32
• Pham, Thi Ngoc Maria Huong; Rinna, Alessandra; Ellingsen, Jan Eirik; Haugen, Håvard Jostein & Reseland, Janne Elin (2015). Enhanced In Vitro HGF Proliferation and Differentiation on Surface Modified Hydrofluoric Acid treated TiO₂.
• Pham, Thi Ngoc Maria Huong; Rinna, Alessandra; Haugen, Håvard Jostein; Ellingsen, Jan Eirik & Reseland, Janne Elin (2015). Enhanced In Vitro HGF Proliferation and Differentiation on Surface Modified Hydrofluoric Acid treated TiO₂.
• Rumian, Lucja; Tiainen, Hanna; Posadowska, Urszula; Brzychczy-Włoch, Monika; Haugen, Håvard Jostein & Pamula, Elzbieta (2015). Ceramic scaffolds containing gentamicin sulphate loaded poly(lactic-co-glycolic acid) microparticles for bone tissue engineering.
• Schweikle, Manuel; Tiainen, Hanna & Haugen, Håvard Jostein (2015). Development of poly(lactic-co-glycolic acid)-based nanoparticles as a drug delivery system for bone regeneration implants.
• Schweikle, Manuel; Tiainen, Hanna & Haugen, Håvard Jostein (2015). Poly(lactic-co-glycolic acid)-based nanoparticles as drug delivery systems for doxycycline hyclate and simvastatin for the treatment of inflammation-caused bone resorption.
• Tiainen, Hanna; Geissler, Sebastian; Lund, Reidar & Haugen, Håvard Jostein (2015). pH triggered aggregation of a structurally disordered polyproline peptide.
• Tiainen, Hanna; Geissler, Sebastian; Lund, Reidar & Haugen, Håvard Jostein (2015). pH triggered self-assembly and aggregation of a structurally disordered proline-rich polypeptide.
• Wiedmer, David Julian; Tiainen, Hanna & Haugen, Håvard Jostein (2015). Antibacterial debridement strategy for infected permanent dental implants.
• Wiedmer, David; Recklies, Sandra; Bossard, Cedric; Tiainen, Hanna & Haugen, Håvard Jostein (2015). Antibacterial sol-gel coating for ceramic TiO2 scaffolds for bone regeneration.
• Wiedmer, David; Tiainen, Hanna; Sagstuen, Einar & Haugen, Håvard Jostein (2015). TiO2 nanoparticles as antibacterial debridement strategy for permanent infected dental implants.
• Wiig, Elisabeth; Tiainen, Hanna; Lian, Aina-Mari; Mann, Vivek; Sundaresan, Alamelu; Haugen, Håvard Jostein; Daniela, Grimm & Reseland, Janne Elin (2015). Effect of microgravity on bone cells in bioinspired ceramic TiO2 scaffolds.
• Geissler, Sebastian; Frank, Matthias Johannes; Walter, Martin Sebastian; Tiainen, Hanna; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2014). Coating of metal implant materials with strontium.
• Gordeladze, Jan Oxholm; Reseland, Janne Elin; Haugen, Håvard Jostein; Haugen, Sigrid; Stakkestad, Øystein; Johnsen, Gaute Floer; Verket, Anders; Valtieri, Mauro & Møller, Mona (2014). Epigenetic factors involved in the "mineralizing/demineralizing" capability of cell phenotypes: Histone deacetylaces (HDACs/Sirts), transcription factors (TFs), microRNAs, and vitamin K2 (MK-7).
• Pullisaar, Helen; Verket, Anders; Szoke, Krisztina; Tiainen, Hanna; Haugen, Håvard Jostein; Brinchmann, Jan E.; Reseland, Janne Elin & Østrup, Esben (2014). Extracellular matrix coated ceramic scaffold enhance osteoblast differentiation.
• Tiainen, Hanna; Reczyńska, Katarzyna & Haugen, Håvard Jostein (2014). Influence of sintering conditions on the properties of TiO2 bone scaffolds.
• Walter, Martin Sebastian; Frank, Matthias Johannes; Satué, María; Monjo, Marta; Rønold, Hans Jacob; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2014). Erratum; Bioactive implant surface with electrochemically bound doxycycline promotes bone formation markers in vitro and in vivo (Dental Materials (2014) 30:2 (200-214)). Dental Materials.  ISSN 0109-5641.  30(4), s 463 . doi: 10.1016/j.dental.2014.01.015?
• Wiedmer, David; Tiainen, Hanna & Haugen, Håvard Jostein (2014). Antibacterial and antioxidant metal oxide materials for bone regeneration.
• Tiainen, Hanna; Wiedmer, David; Wohlfahrt, Johan Caspar; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2013). Highly porous ceramic TiO2 scaffolds for bone repair.
• Tiainen, Hanna; Wiedmer, David; Wohlfahrt, Johan Caspar; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2013). Highly porous ceramic titanium dioxide scaffolds for bone repair.
• Haugen, Håvard Jostein & Lyngstadaas, Ståle Petter (2013). Like sterke som originalen. Den norske tannlegeforenings tidende.  ISSN 0029-2303.  123, s 730- 731 Vis sammendrag

  Hvis alt går etter planen kan tannlegespesialistene i Norge prøve det nye materialet om to år, sier forskningsleder Håvard Jostein Haugen. Han har forsket frem materialet sammen med professorene Ståle Petter Lyngstadaas og Jan Eirik Ellingsen ved Institutt for klinisk odontologi. - Når pasienten har mistet deler av kjevebenet kan ikke kroppen alltid hele dette av seg selv. Den trenger hjelp av et «vekststativ», sier Haugen. Et vekststativ er forenklet sagt forskaling og armering for det nye benet. - Vi lager porøse vekststativer av titandioksid (TiO2) med passende størrelse for å sette inn i defekte ben. Når vi putter materialet ned i den skadede delen av kjeven, vil benceller vokse og feste seg til veggene i dette materialet. Til slutt blir det som et nytt ben, like sterkt som originale

• Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter & Verket, Anders (2013). Tannleger uten framtidsskrekk. Forskning.no : nettavis med nyheter fra norsk og internasjonal forskning.
• Müller, Benjamin; Wengenroth, Jonas; Tiainen, Hanna; Haugen, Håvard Jostein & Lyngstadaas, Ståle Petter (2013). Bone-structural mimicry of TiO2 scaffolds for regeneration of alveolar defects.
• Müller, Benjamin; Wengenroth, Jonas; Tiainen, Hanna; Haugen, Håvard Jostein & Lyngstadaas, Ståle Petter (2013). TiO2 Scaffolds with Cortical Bone Imitation for Enhanced Alveolar Bone Defect Healing.
• Müller, Benjamin; Wengenroth, Jonas; Tiainen, Hanna; Haugen, Håvard Jostein & Lyngstadaas, Ståle Petter (2013). TiO2 scaffolds with pore size gradient to avoid soft tissue ingrowth in alveolar defects.
• Petzold, Christiane; Haugen, Håvard Jostein & Karlis, Gross (2013). Designing hydroxyapatite coating topography at the micro and nano level.
• Pham, Thi Ngoc Maria Huong; Landin, Maria Augusta Dos S Silva; Tiainen, Hanna; Reseland, Janne Elin; Ellingsen, Jan Eirik & Haugen, Håvard Jostein (2013). The Effect Of Hydrofluoric Acid Treatment Of Titanium And Titanium Dioxide Surface on Primary Human Osteoblasts.
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Reseland, Janne Elin & Østrup, Esben (2013). Coating titanium dioxide scaffold with simvastatin in alginate promote osteoblast differentiation in vitro.
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Reseland, Janne Elin & Østrup, Esben (2013). Enhanced in vitro bone differentiation on TiO₂ scaffold coated with simvastatin.
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Reseland, Janne Elin & Østrup, Esben (2013). Local delivery of simvastatin enhances bone differentiation on porous titanium dioxide scaffold.
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Reseland, Janne Elin & Østrup, Esben (2013). Local delivery of simvastatin on titanium dioxide scaffolds; a tissue engineering model.
• Walter, Martin Sebastian; Frank, Matthias Johannes; Rubert, Marina; Monjo, Marta; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2013). Simvastatin bound to grit blasted and acid etched titanium zirconium by anodic oxidation increased alkaline phosphatase, collagen type I and osteocalcin expression in vitro.

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