Håvard Jostein Haugen

• Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter; Rossi, Filippo & Perale, Giuseppe (2019). Bone grafts: which is the ideal biomaterial?. Journal of Clinical Periodontology.  ISSN 0303-6979.  46(21), s 92- 102 . doi: 10.1111/jcpe.13058 Full text in Research Archive. Show summary

  Abstract Bovine xenograft materials, followed by synthetic biomaterials, which unfortunately still lack documented predictability and clinical performance, dominate the market for the cranio‐maxillofacial area. In Europe, new stringent regulations are expected to further limit the allograft market in the future Aim Within this narrative review, we discuss possible future biomaterials for bone replacement. Scientific Rationale for Study Although the bone graft (BG) literature is overflooded, only a handful of new BG substitutes are clinically available. Laboratory studies tend to focus on advanced production methods and novel biomaterial features, which can be costly to produce. Practical Implications In this review, we ask why such a limited number of BGs are clinically available when compared to extensive laboratory studies. We also discuss what features are needed for an ideal BG. Results We have identified the key properties of current bone substitutes and have provided important information to guide clinical decision‐making and generate new perspectives on bone substitutes. Our results indicated that different mechanical and biological properties are needed despite each having a broad spectrum of variations. Conclusions We foresee bone replacement composite materials with higher levels of bioactivity, providing an appropriate balance between bioabsorption and volume maintenance for achieving ideal bone remodelling.

• Klemm, Anne; Gomez-Florit, Manuel; Almeida Carvalho, Patricia; Wachendörfer, Mattis; Gomes, Manuela E.; Haugen, Håvard Jostein & Tiainen, Hanna (2019). Grain boundary corrosion in TiO2 bone scaffolds doped with group II cations. Journal of the European Ceramic Society.  ISSN 0955-2219.  39, s 1577- 1585 . doi: 10.1016/j.jeurceramsoc.2018.12.055
• Pham, Thi Ngoc Maria Huong; Haugen, Håvard Jostein; Rinna, Alessandra; Ellingsen, Jan Eirik & Reseland, Janne Elin (2019). Hydrofluoric acid treatment of titanium surfaces enhance the proliferation of human gingival fibroblasts. Journal of Tissue Engineering.  ISSN 2041-7314.  10 . doi: 10.1177/2041731419828950 Show summary

  The attachment of implants rely on bone and soft tissue biocompatibility. The aim was to investigate the effect of fluoride modified metallic titanium (Ti) surfaces (Ti-F) on proliferation and differentiation of human gingival fibroblasts (HGF). HGF cells were exposed to hydrofluoric acid (HF) modified Ti coins (Ti-F) for 1, 3, 7, 14 and 21d, and untreated coins were used as controls. A 5-6 fold increase in the proliferation of HGF on Ti-F compared to Ti surfaces was observed. Enhanced gene expression of IL-6 and OPG was found at 7 d. Increased levels of sclerostin, IL- 6 and OPG in the media from HGF cultured on Ti-F coins were found compared to controls. Our results confirm that HF modified surface may indirectly enhance the firm attachment of implant surface to junction epithelium, soft tissue epithelium, which would give protection for underlying osseous structures making osseointegration of the dental implant possible.

• Sanz, Mariano; Dahlin, Christer; Apatzidou, Danae; Artzi, Zvi; Bozic, Darco; Calciolari, Elena; De Bruyn, Hugo; Dommisch, Henrik; Donos, Nicos; Eickholz, Peter; Ellingsen, Jan Eirik; Haugen, Håvard Jostein; Herrera, David; Lambert, France; Layrolle, Pierre; Montero, Eduardo; Mustafa, Kamal Babikeir Eln; Omar, Omar & Schliephake, Henning (2019). Biomaterials and regenerative technologies used in bone regeneration in the craniomaxillofacial region: Consensus report of group 2 of the 15th European Workshop on Periodontology on Bone Regeneration. Journal of Clinical Periodontology.  ISSN 0303-6979.  46(21), s 82- 91 . doi: 10.1111/jcpe.13123
• Schweikle, Manuel; Bjørnøy, Sindre Hove; Van Helvoort, Antonius; Haugen, Håvard Jostein; Sikorski, Pawel & Tiainen, Hanna (2019). Stabilisation of amorphous calcium phosphate in polyethylene glycol hydrogels. Acta Biomaterialia.  ISSN 1742-7061.  90, s 132- 145 . doi: 10.1016/j.actbio.2019.03.044 Show summary

  Acellular polymer-calcium phosphate composites are promising bone graft materials. Hydrogels are suitable for providing a temporary matrix, while calcium phosphate minerals serve as ion depots for calcium and phosphate required for de novo bone formation. Crystalline calcium phosphates are stable under biological conditions and are commonly used in such scaffolds. However, the low solubility of these phases reduces the availability of free ions and potentially obstructs the remodelling necessary for the formation of mineralised tissue. Here, we investigate two different strategies to stabilise amorphous calcium phosphates in a synthetic polyethylene glycol-based hydrogel matrix. In vitro experiments mimicking an injectable application showed that amorphous calcium phosphate (ACP) of variable stability was formed in the hydrogel matrices. In additive-free composites, ACP transformed into brushite within minutes. Citrate or zinc additives were found to stabilise the formed ACP phase to different degrees. In the presence of citrate, ACP was stable for at least 2 h before it transformed into hydroxyapatite within 3–20 days. Partial calcium substitution with zinc (Zn/Ca = 10%) produced zinc-doped ACP of high stability that did not show signs of crystallisation for at least 20 days. The presented methods and findings open new possibilities for the design of novel injectable synthetic bone graft materials. The possibility to produce ACP with tailorable stability promises great potential for creating temporary scaffolds with good osteogenic properties. Statement of significance Synthetic hydrogel-calcium phosphate (CaP) composites are promising biomaterials to replace human- and animal-derived bone scaffolds. Most reported hydrogel-CaP composite materials employ crystalline CaP phases that lack the osteoinductive properties of autograft. Stabilising amorphous calcium phosphates (ACP) could overcome this limitation, readily delivering calcium and phosphate ions and facilitating remodelling into new bone tissue. The design of synthetic hydrogel-ACP scaffolds, however, requires more understanding of the mineralisation processes in such matrices. This study presents a model system to characterise the complex mineral formation and transformation processes within a hydrogel matrix. We demonstrate a facile route to produce self-mineralising injectable synthetic hydrogels and prove two different strategies to stabilise ACP for different periods within the formed composites.

• Tanzi, Maria Cristina; gantz, daniel; Bertoldi, Serena; negrini, Nicola Contessi & Haugen, Håvard Jostein (2019). Polymers and Scaffolds with Improved Blood Compatibility and Enhanced Cellular Response with Focus on Polyurethane Foams Functionalized with Amino-Amide Groups. Journal of Advanced Biotechnology and Bioengineering.  ISSN 2311-1755.  7, s 18- 29 . doi: 10.12970/2311-1755.2019.07.03 Show summary

  Biofunctionalization of biomaterial substrates has gained increasing interest in Tissue Engineering (TE) to create functional scaffolds with improved performances and capable of directing cellular behaviour. This work takes into account the functionalization of polyurethane (PU) foams with an active molecule, the diamino-diamide diol PIME, purposely designed to be inserted in the structure of linear PUs and previously found to be able to improve hemo-, cytocompatibility and bacterial resistance of these biomaterials. Here, for the first time, the gas foaming process previously set up for biocompatible PU foams was modified, and different methods were tested to obtain structurally stable foams containing PIME. The obtained foams and respective controls showed appropriate porosity (Ø = 407 ÷ 589 ± 30 m; > 90% open porosity), similar density ( 0.14 g/cm3) and hydrophilicity (water uptake  300%) and adequate compressive properties (E = 0.058 ÷ 0.170 Mpa; Hysteresis Area = 2.07 ÷ 5.59 x 10-3 J/cm3, < 5% residual deformation). PU foams containing PIME exhibited a more spherical pore geometry; the foam obtained by applying a higher stirring speed during synthesis (PU-3kP) exhibited a lower mean pore size and an elastic modulus higher than that of the other foams. FT-IR spectroscopy indicated the presence of new absorption bands and structural changes attributable to the presence of PIME. Cytotoxicity tests performed with the cell line L929 verified the absence of cytotoxic effects. All foams were able to support L929 fibroblasts proliferation and vitality for seven days; PIME-containing foams showed higher values of cell proliferation (p<0.05) that the respective controls. Keywords: Polyurethane foams, scaffold, functionalization, bioactive molecule, PIME, open porosity, compressive properties, cell interactions, L929, fibroblasts.

• Zhang, Xianbin; Tiainen, Hanna & Haugen, Håvard Jostein (2019). 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.  57(1), s 311- 324 . doi: 10.1007/s11517-018-1884-2 Full text in Research Archive. Show summary

  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.

• Zhu, Hao; Xiongfa, Ji; Hanfeng, Guan; Liming, Zhao; Libo, Zhao; Changyu, Liu; Cong, Cai; Weijing, Li; Tenghui, Tao; Reseland, Janne Elin; Haugen, Håvard Jostein & Xiao, Jun (2019). Tantalum Nanoparticles Reinforced Polyetheretherketone Shows Enhanced Bone Formation. Materials Science and Engineering C: Materials for Biological Applications.  ISSN 0928-4931. . doi: 10.1016/j.msec.2019.03.091 Show summary

  Polyetheretherketone (PEEK) has been used in orthopedic surgery for several decades. Numerous methods were invented to alter the property of PEEK. By adding nanoparticles, fibers, elastic modulus and strength of PEEK can be changed to meet certain demand. In this study, tantalum (Ta), a promising metal, was introduced to modify the properties of PEEK, in which PEEK was reinforced with different contents of tantalum nanoparticles (from 1%wt to 9%wt). Mechanical properties and biological functions (both in vitro and in vivo) were then investigated. The highest elastic modulus and compressive strength were observed in 3%Ta-PEEK. Cell experiments as cell adhesion, collagen secretion, biomineralization and osteogenesis related gene expression showed preferable results in 3%Ta-PEEK and 5%Ta-PEEK. Improved bone integration was shown in 3%Ta-PEEK and 5%Ta-PEEK in vivo. Above all, enhanced mechanical properties and promoted bone formation were proved for 3%Ta-PEEK and 5%Ta-PEEK compared to others groups both in vivo and in vitro, suggesting that the addition of tantalum nanoparticles modified the osseointegration ability of PEEK. This composite of tantalum and PEEK could have a clinical potential for orthopedic implants.

• 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(8), s 942- 951 . doi: 10.1111/iej.12902 Full text in Research Archive. Show summary

  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 Nano Materials.  ISSN 2574-0970.  1, s 4190- 4197 . doi: 10.1021/acsanm.8b00938 Show summary

  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.

• Virto, Leire; 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.  53(5), s 825- 831 . doi: 10.1111/jre.12571 Full text in Research Archive. Show summary

  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.

• Virto, Leire; Cano, Pilar; Jiménez-ortega, Vanesa; Fernández-mateos, Pilar; González, Jerián; Haugen, Håvard Jostein; Esquifino, Ana isabel & Sanz Alonso, Mariano (2018). Melatonin as adjunctive therapy in the treatment of periodontitis associated with obesity. Journal of Clinical Periodontology.  ISSN 0303-6979.  45(11), s 1336- 1346 . doi: 10.1111/jcpe.13013 Show summary

  Aims To study the effect of adjunctive systemic administration of melatonin to standard mechanical periodontal therapy in obese rats with experimental periodontitis. Materials and methods In 42 Wistar rats with an initial body weight of 180 g., half (n=21) were fed with a high‐fat diet to induce obesity. In both obese and normal‐weight groups, experimental periodontitis was subsequently induced through oral gavages with a combination of Porphyromona gingivalis and Fusobacterium nucleatum. Both groups were randomly allocated to either, no treatment or periodontal treatment consisting on standard mechanical debridement, with either adjunctive chlorhexidine or melatonin. Outcomes were evaluated by the changes in clinical parameters (probing depth modified gingival index, plaque dental index and bleeding on probing), in bone resorption and in the levels of biomarkers in plasma and in gingival tissue (inflammatory cytokines, insulin, leptin, osteocalcin, osteopontin, plasminogen activator inhibitor‐1, intercellular adhesion molecule 1, E‐selectin and lipids). Results In the obese‐periodontitis group, adjunctive melatonin administration resulted in reduced gingival inflammation and bleeding on probing, with significant reductions in probing depth and enhanced bone repair demonstrated by Micro‐CT (15% reduction in alveolar bone destruction) when compared with the same group treated with adjunctive CHX or the normal‐weight rats with either melatonin or CHX. In this melatonin‐treated obese‐periodontitis group, a significant impact on biochemical biomarkers was also demonstrated in both gingival and plasma samples, when compared with the other groups, with significant reductions in pro‐inflammatory cytokines. Conclusions Adjunctive melatonin therapy significantly reduced alveolar bone loss and exerted a protective anti‐inflammatory effect mainly in those experimental animals affected by the co‐morbidity of periodontitis and obesity.

• 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 Full text in Research Archive.
• 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 Show summary

  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 Show summary

  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 Show summary

  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 Show summary

  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 Show summary

  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 Show summary

  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 Show summary

  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 Show summary

  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.

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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. Show summary

  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. Show summary

  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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• Rahmati, Maryam; Blaker, Jonathan James; Lyngstadaas, Ståle Petter; Mano, Joao F. & Haugen, Håvard Jostein (2020). Designing multigradient biomaterials for skin regeneration. Materials Today.  ISSN 1369-7021.  5 . doi: 10.1016/j.mtadv.2019.100051 Show summary

  Skin defects are amongst the main causes of morbidity and mortality worldwide, which account for significantly high socioeconomic costs. Today, much attention is being paid to tissue engineering and biomaterials strategies for skin regeneration, and among them, there is increasing interest in using multigradient biomaterials. Gradient-based approaches are an emerging trend in tissue engineering for the homogeneous delivery of therapeutic agents by using biomaterials. Several studies have acknowledged that wound repair mechanisms could be enhanced through biomimicking physicochemical properties of different skin layers. In addition, in different layers of skin tissue, cells experience various physicochemical gradients, which potentially regulate their behaviors. Therefore, interface tissue engineering and biomaterials approaches are gaining increasing attention for skin regeneration through the incorporation of physicochemical gradients within the engineered constructs. This review first presents a necessary overview of the biological properties of skin tissue and its changes during repair in different tissue injuries. Fundamental issues and necessities of using different types of gradient scaffolds and interface tissue engineering strategies for skin regeneration are addressed. The focus of this review is on describing current progress in designing gradient scaffolds for controlling and directing cellular and molecular responses in skin tissue. The main used fabrication approaches, including both traditional and advanced methods for designing multigradient scaffolds, are also discussed.

• Haugen, Håvard Jostein (2019). Experimental Peri-implantitis around Titanium Implants with a Modified Titanium Surface with a Phosphonic Acid Monolayer. NanoCT Results of an Experimental In-vivo Investigation.
• Haugen, Håvard Jostein (2019). Micro and nano-CT applied to dental research.
• Haugen, Håvard Jostein (2019). Micro-porosities Revealed in Hybrid Dental Composites by Nano X-ray Tomography.
• Haugen, Håvard Jostein (2019). Novel nano-computed tomography techniques applied to dental research.
• Haugen, Håvard Jostein (2019). Structural and Bio-inspired Bioceramic Materials and Implants.
• Pawlik, A; Sulka, G.D. & Haugen, Håvard Jostein (2019). Fabrication and characterization of doxycycline-coated nanoporous TiO2 layers.
• Tanzi, Maria Cristina; gantz, daniel; Bertoldi, Serena; negrini, Nicola Contessi & Haugen, Håvard Jostein (2019). FUNCTIONALIZED POLYURETHANE FOAMS AS TISSUE SCAFFOLDS WITH ENHANCED CELLULAR RESPONSE. Show summary

  Recentadvancementsintissueengineeringrequirethedevelopmentoftailoredscaffoldswithphysicochemicalcuesabletopromotespecificandpositiveresponsesoncellsofthetargettissue • Biomedicalpolyurethanes(PU)exhibitgoodresilienceandfatiguestrength,goodcytoandhemocompatibilityandlowbacteriaadhesion;PUfoamscanbedesignedassuitablescaffoldsintissueengineering[1-3] • The diamino-diamide diolPIME (figure)canform stable complexes with heparin, due to the protonation of its tertiary amino groups at a physiological pH, has excellent cytocompatibility and can promote cells adhesion and proliferation on linear PUs containing

• de Lange, Thomas; Haugen, Håvard Jostein & Møystad, Anne (2018). Digital Prospects of Formative and Summative Assessment in Dental Education: Technological Opportunities and Challenges. Show summary

  Abstract: It is a well-known fact that assessment is an important driver for student learning. In the advancement of digital technologies, the question is how digital resources can be used to improve formative and summative assessment in ways that support student learning as well as ensuring knowledge standards for future dental professionals. Two experimental studies on digital assessment have been conducted at the Faculty of Dentistry, University of Oslo. Firstly, digitized formative assessment based on Multiple Choice questionnaires (MCQ) was implemented in testing students’ knowledge from prior parts of their education. Secondly, a pilot-study of a digitized summative assessment in oral radiology was conducted to identify benefits and challenges in applying entirely digital based exams. Results from these experiments are presented and discussed in relation to research on assessment and student learning.

• Haugen, Håvard Jostein & Ellingsen, Jan Eirik (2018, 30. august). Her skapes fremtidens arbeidsplasser i bioteknologi. [Fagblad].  Apollon. Show summary

  I det nye laboratoriet Sharelab på Blindern møtes forskere, bedriftsutviklere og investorer. De håper å skape hundrevis av kommersielle arbeidsplasser innen bioteknologi.

• Haugen, Håvard Jostein & Reseland, Janne Elin (2018). In vivo performance of a highly porous titanium dioxide bone scaffold and its way to the medical device market.
• Haugen, Håvard Jostein; Reseland, Janne Elin & Gomez-Florit, Manuel (2018). The effect of IDP coated biomaterial.
• Klemm, Anne; Haugen, Håvard Jostein & Tiainen, Hanna (2018). Grain boundary corrosion in Sr and Ca doped TiO2 bone scaffold. Show summary

  Porous TiO2 scaffolds as a bone support structure showed high porosity combined with high compressive strength1. Doping ceramic scaffolds with Ca or Sr leads to even higher compressive strength and formation of impurity rich grain boundaries2. Grain boundary dissolution can occur during bone healing, because of a local pH drop3. To improve the corrosion resistance of cationic doped TiO2 scaffolds, the objective of this study was to investigate the corrosion depending on doping concentration to evaluate corrosion mechanisms.

• Schweikle, Manuel; Bjørnøy, Sindre Hove; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Van Helvoort, Antonius; Sikorski, Pawel & Tiainen, Hanna (2018). Self-mineralising synthetic injectable hydrogels for bone repair.
• Gomez-Florit, Manuel; Reseland, Janne Elin & Haugen, Håvard Jostein (2017). Synthetic intrinsically-disordered-peptides for bone tissue engineering. Show summary

  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.

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