Håvard Jostein Haugen

• Wang, Zhule; Nogueira, Liebert Parreiras; Haugen, Håvard Jostein; Van Der Geest, Ingrid CM.; de Almeida Rodrigues, Patricia Caetano & Janssen, Dennis [Show all 9 contributors for this article] (2021). Dual-functional porous and cisplatin-loaded polymethylmethacrylate cement for reconstruction of load-bearing bone defect kills bone tumor cells. Bioactive Materials. ISSN 2452-199X. doi: 10.1016/j.bioactmat.2021.12.023.
• Rahmati, Maryam; Stoetzel, Sabine; El Khassawna, Thaqif; Mao, Chenyi; Ali, Adilijiang & Vaughan, Joshua C. [Show all 14 contributors for this article] (2021). Intrinsically disordered peptides enhance regenerative capacities of bone composite xenografts . Materials Today. ISSN 1369-7021. doi: 10.1016/j.mattod.2021.12.001. Show summary

  Biomaterial scientists design organic bone substitutes based on the biochemical properties of the mimicked tissue to achieve near native functionality. Several non-collagenous proteins in bone are known as intrinsically disordered proteins (IDPs), as they lack detectible ordered domains and a fixed 3D structure under physiological conditions. Many IDPs perform regulatory roles in a range of cellular functions, which motivated us to design two proline-rich disordered peptides (P2 and P6) and augmented them into the SmartBone® (SBN) biohybrid substitute. Recently we reported an improved proliferation and osteogensis of human osteoblasts and mesenchymal stem cells in the composite groups containing peptides (named here as SBN + P2 and SBN + P6) in vitro. To address the effects of these composites on bone formation and biomineralization, this in vivo study investigated their functions in critical size craniotomy defects in 16 domestic pigs after 8 and 16 weeks of healing. For this purpose, we used cone beam computed tomography (CBCT), microCT (µCT), histology, immunohistochemistry, fluorescent labeling of abundant reactive entities (FLARE), synchrotron SAXS/XRD, optical photothermal IR (O-PTIR) microscopy and nanoscale atomic force microscopy-infrared (AFM-IR) analyses. Our results represent new synthetic IDPs as potential candidates for directing bone formation and biomineralization. The SBN + P6 stimulated significantly higher bone formation and biomineralization after 8 weeks of healing compared to other groups indicating its potential in stimulating early biomineralization. After 16 weeks of healing, the SBN + P2 induced significantly higher bone formation and biomineralization compared to other groups indicating its effects on later bone formation and biomineralization processes. The vigorous stretching of amide primary and secondary IR absorbance peaks at 1660 and 1546 cm−1 in the SBN + P2 group verified that this peptide experienced more conformational changes after 16 weeks of implantation with a higher phosphate intensity at 1037 cm−1 compared to peptide 6. Overall, P2 and P6 are promising candidates for bone augmentation strategies in critical clinical applications. We concluded that FLARE and O-PTIR are promising tools in evaluating and diagnosing the biochemical structure of bone tissue and the bone-biomaterial interface.

• Wang, Zhule; Parreiras Nogueira, Liebert; Haugen, Håvard Jostein; Van Der Geest, Ingrid C M; Caetano de Almeida Ro, Patricia & Janssen, Dennis [Show all 9 contributors for this article] (2021). Dual-purpose porous Polymethylmethacrylate Cement Loaded with Cisplatin Kills Bone Tumor Cells. Bioactive Materials. ISSN 2452-199X. doi: 10.1016/j.bioactmat.2021.12.023.
• Bakkalci, Deniz; Jay, Amrita; Rezaei, Azadeh; Howard, Christopher A.; Haugen, Håvard Jostein & Pape, Judith [Show all 12 contributors for this article] (2021). Bioengineering the ameloblastoma tumour to study its efect on bone nodule formation. Scientific Reports. ISSN 2045-2322. 11(24088 ). doi: 10.1038/s41598-021-03484-5. Show summary

  Ameloblastoma is a benign, epithelial cancer of the jawbone, which causes bone resorption and disfigurement to patients affected. The interaction of ameloblastoma with its tumour stroma drives invasion and progression. We used stiff collagen matrices to engineer active bone forming stroma, to probe the interaction of ameloblastoma with its native tumour bone microenvironment. This bone-stroma was assessed by nano-CT, transmission electron microscopy (TEM), Raman spectroscopy and gene analysis. Furthermore, we investigated gene correlation between bone forming 3D bone stroma and ameloblastoma introduced 3D bone stroma. Ameloblastoma cells increased expression of MMP-2 and -9 and RANK temporally in 3D compared to 2D. Our 3D biomimetic model formed bone nodules of an average surface area of 0.1 mm2 and average height of 92.37 ± 7.96 μm over 21 days. We demonstrate a woven bone phenotype with distinct mineral and matrix components and increased expression of bone formation genes in our engineered bone. Introducing ameloblastoma to the bone stroma, completely inhibited bone formation, in a spatially specific manner. Multivariate gene analysis showed that ameloblastoma cells downregulate bone formation genes such as RUNX2. Through the development of a comprehensive bone stroma, we show that an ameloblastoma tumour mass prevents osteoblasts from forming new bone nodules and severely restricted the growth of existing bone nodules. We have identified potential pathways for this inhibition. More critically, we present novel findings on the interaction of stromal osteoblasts with ameloblastoma.

• Thieu, Minh Khai Le; Homayouni, Amin; Hæren, Lena Ringsby; Tiainen, Hanna; Verket, Anders & Ellingsen, Jan Eirik [Show all 13 contributors for this article] (2021). Impact of simultaneous placement of implant and block bone graft substitute: an in vivo peri-implant defect model. Biomaterials Research. ISSN 2055-7124. 25(43). doi: 10.1186/s40824-021-00245-3. Full text in Research Archive
• Hussain, Badra; Karaca, Ebru Ozkan; Kuru, Bahar Eren; Gursoy, Hare; Haugen, Håvard Jostein & Wohlfahrt, Johan Caspar (2021). Treatment of residual pockets using an oscillating chitosan device versus regular curettes alone—a randomized, feasibility parallel-arm clinical trial. Journal of Periodontology. ISSN 0022-3492. doi: 10.1002/JPER.21-0496.
• Hussain, Badra; Haugen, Håvard Jostein; Aass, Anne Merete; Sanz, Mariano; Antonoglou, Georgios & Bouchard, Philippe [Show all 23 contributors for this article] (2021). Peri-Implant Health and the Knowing-Doing Gap—A Digital Survey on Procedures and Therapies. Frontiers in Dental Medicine. ISSN 2673-4915. 2(726607). doi: 10.3389/fdmed.2021.726607. Full text in Research Archive
• Rahmati, Maryam; Stötzel, Sabine; El Khassawna, Thaqif; Iskhahova, Kamila; Wieland, D.C. Florian & Plumhoff, Berit Zeller [Show all 7 contributors for this article] (2021). Early Osteoimmunomodulatory Effects of Magnesium–Calcium–Zinc alloys. Journal of Tissue Engineering. ISSN 2041-7314. doi: 10.1177/20417314211047100. Full text in Research Archive Show summary

  Today, substantial attention is given to biomaterial strategies for bone regeneration, and among them, there is a growing interest in using immunomodulatory biomaterials. The ability of a biomaterial to induce neo vascularization and macrophage polarization is a major factor in defining its success. Magnesium (Mg)-based degradable alloys have attracted significant attention for bone regeneration owing to their biodegradability and potential for avoiding secondary removal surgeries. However, there is insufficient evidence in the literature regarding the early inflammatory responses to these alloys in vivo. In this study, we investigated the early body responses to Mg 0.45 wt%Zn-0.45 wt%Ca pin-shaped alloy (known as ZX00 alloy) in rat femora 2, 5 and 10 days after implantation. We used 3D micro computed tomography (μCT), histological, immunohistochemical, histomorphometrical and small angle X-ray scattering (SAXS) analyses to study new bone formation, early macrophage polarization, neo vascularization and bone quality at the implant bone interface. The expression of macrophage type 2 biological markers increased significantly after 10 days of Mg alloy implantation, indicating its potential in stimulating macrophage polarization. Our biomineralization results using μCT as well as histological stained sections did not indicate any statistically significant differences between different time points for both groups. The activity of alkaline phosphatase (ALP) and Runt-related transcription factor 2 (Runx 2) biological markers decreased significantly for Mg group, indicating less osteoblast activity. Generally, our results supported the potential of ZX00 alloy to enhance the expression of macrophage polarization in vivo; however, we could not observe any statistically significant changes regarding biomineralization.

• Palombo, David; Rahmati, Maryam; Vignoletti, Fabio; Esporrin, Javier Sanz; Haugen, Håvard Jostein & Sanz, Mariano (2021). Hard and soft tissue healing around implants with a modified implant neck configuration: an experimental in vivo preclinical investigation. Clinical Oral Implants Research. ISSN 0905-7161. doi: 10.1111/clr.13812.
• Marovic, Danijela; Haugen, Håvard Jostein; Mandic, Visnja Negovetic; Par, Matej; Zheng, Kai & Tarle, Zrinka [Show all 7 contributors for this article] (2021). Incorporation of Copper-Doped Mesoporous Bioactive Glass Nanospheres in Experimental Dental Composites: Chemical and Mechanical Characterization. Materials. ISSN 1996-1944. 14(2611), p. 1–12. doi: 10.3390/ma14102611. Full text in Research Archive
• D. Tien, Nguyen; Lyngstadaas, Ståle Petter; Mano, Joao F.; Blaker, Jonathan James & Haugen, Håvard Jostein (2021). Recent Developments in Chitosan-Based Micro/Nanofibers for Sustainable Food Packaging, Smart Textiles, Cosmeceuticals, and Biomedical Applications. Molecules. ISSN 1420-3049. 26(2683), p. 1–24. doi: 10.3390/molecules26092683. Full text in Research Archive
• Hildebrand, Torben; Nogueira, Liebert Parreiras; Sunde, Pia Titterud; Ørstavik, Dag; Glasmacher, Birgit & Haugen, Håvard Jostein (2021). Contrast-enhanced nano-CT reveals dental soft tissues and cellular layers. International Endodontic Journal. ISSN 0143-2885. doi: 10.1111/iej.13527. Full text in Research Archive
• Zhu, Hao; Haugen, Håvard Jostein; Perale, Giuseppe; Reseland, Janne Elin; Nogueira, Liebert Parreiras & Cantalapiedra, Antonio gonzalez [Show all 11 contributors for this article] (2021). Tailoring Resorption Rates and Osteogenic Response in Xeno-Hybrid Bone Grafts: The Effect of Added Gelatins. Engineering. ISSN 2095-8099. doi: 10.1016/j.eng.2021.01.010. Full text in Research Archive
• Thieu, Minh Khai Le; Haugen, Håvard Jostein; Esporrin, Javier Sanz; Sanz, Mariano; Lyngstadaas, Ståle Petter & Verket, Anders (2021). Guided bone regeneration of chronic non-contained bone defects using a volume stable porous block TiO2 scaffold: An experimental in vivo study. Clinical Oral Implants Research. ISSN 0905-7161. doi: 10.1111/clr.13708.
• Di Raimondo, Ricardo; Sanz, Javier; Sanz Martin1, Ignacio; Vignoletti, Fabio; Nuñez, Javi & Muñoz, Fernando [Show all 8 contributors for this article] (2021). Hard tissue volumetric and soft tissue contour linear changes at implants with different surface characteristics after experimentally induced peri-implantitis: an experimental in vivo investigation. Clinical Oral Investigations. ISSN 1432-6981. doi: 10.1007/s00784-020-03720-8. Show summary

  Objective To evaluate the hard tissue volumetric and soft tissue contour linear changes in implants with two different implant surface characteristics after a ligature-induced peri-implantitis. Material andmethods In eight beagle dogs, implants with the same size and diameter but distinct surface characteristics were placed in the healed mandibular sites. Test implants had an external monolayer of multi-phosphonate molecules (B+), while control implants were identical but without the phosphonate-rich surface. Once the implants were osseointegrated, oral hygiene was interrupted and peri-implantitis was induced by placing subgingival ligatures. After 16 weeks, the ligatures were removed and peri-implantitis progressed spontaneously. Bone to implant contact (BIC) and bone loss (BL) were assessed three-dimensionally with Micro-Ct (μCT). Dental casts were optically scanned and the obtained digitalized standard tessellation language (STL) images were used to assess the soft tissue vertical and horizontal contour linear changes. Results Reduction of the three-dimensional BIC percentage during the induction and progression phases of the experimental peri-implantitis was similar for both the experimental and control implants, without statistically significant differences between them. Soft tissue analysis revealed for both implant groups an increase in horizontal dimension after the induction of peri-implantitis, followed by a decrease after the spontaneous progression period. In the vertical dimension, a soft tissue dehiscence was observed in both groups, being more pronounced at the buccal aspect. Conclusions The added phosphonate-rich surface did not provide a more resistant environment against experimental periimplantitis, when assessed by the changes in bone volume and soft tissue contours. Clinical relevance Ligature-induced peri-implantitis is a validated model to study the tissue changes occurring during peri-implantitis. It was hypothesized that a stronger osseointegration mediated by the chemical bond of a phosphonaterich implant surface would develop an environment more resistant to the inflammatory changes occurring after experimental peri-implantitis. These results, however, indicate that the hard and soft tissue destructive changes occurring at both the induction and progression phases of experimental peri-implantitis were not influenced by the quality of osseointegration.

• Vyas, Cian; Zhang, Jun; Øvrebø, Øystein; Huang, Boyang; Roberts, Iwan & Setty, Mohan [Show all 10 contributors for this article] (2021). 3D printing of silk microparticle reinforced polycaprolactone scaffolds for tissue engineering applications. Materials Science and Engineering C: Materials for Biological Applications. ISSN 0928-4931. 118. doi: 10.1016/j.msec.2020.111433. Full text in Research Archive
• Sukul, Mousumi; Sahariah, Priyanka; Lauzon, Hélène L.; Borges, João; Másson, Már & Mano, Joao F. [Show all 8 contributors for this article] (2021). In vitro biological response of human osteoblasts in 3D chitosan sponges with controlled degree of deacetylation and molecular weight. Carbohydrate Polymers. ISSN 0144-8617. 254. doi: 10.1016/j.carbpol.2020.117434. Full text in Research Archive
• Zhu, Hao; Blahnová, Veronika Hefka; Perale, Giuseppe; Xiao, Jun; Betge, Felice & Boniolo, Fabio [Show all 9 contributors for this article] (2020). Xeno-Hybrid Bone Graft Releasing Biomimetic Proteins Promotes Osteogenic Differentiation of hMSCs. Frontiers in Cell and Developmental Biology. ISSN 2296-634X. doi: 10.3389/fcell.2020.619111. Full text in Research Archive
• Kallas, Pawel; Haugen, Håvard Jostein; Gadegaard, Nikolaj; Stormonth-Darling, John; Hulander, Mats & Andersson, Martin [Show all 7 contributors for this article] (2020). Adhesion of Escherichia Coli to Nanostructured Surfaces and the Role of Type 1 Fimbriae. Nanomaterials. ISSN 2079-4991. 10(11). doi: 10.3390/nano10112247. Full text in Research Archive
• Gross, Karlis Agris; Petzold, Christiane; Pluduma, Liene; Kumermanis, Maris & Haugen, Håvard Jostein (2020). Structural and Chemical Hierarchy in Hydroxyapatite Coatings . Materials. ISSN 1996-1944. 13(4447), p. 1–15. Full text in Research Archive Show summary

  Hydroxyapatite coatings need similarly shaped splats as building blocks and then a homogeneous microstructure to unravel the structural and chemical hierarchy for more refined improvements to implant surfaces. Coatings were thermally sprayed with differently sized powders (20-40, 40-63 and 63-80 µm) to produce flattened homogeneous splats. The surface was characterized for splat shape by profilometry and AFM, crystal size by AFM, crystal orientation by X-ray diffraction (XRD) and structural variations by XRD. Chemical composition was assessed by phase analysis, but variations in chemistry were detected by XRD and Raman spectroscopy. The resulting surface electrical potential was measured by Kelvin probe AFM. Five levels of structural hierarchy were suggested: the coating, the splat, oriented crystals, alternate layers of oxyapatite and HAp, and the suggested anion orientation. Chemical hierarchy was present over a lower range of order for smaller splats. Coatings made from smaller splats exhibited a greater electrical potential, inferred to arise from oxyapatite, and supplemented by ordered OH- ions in a rehydroxylated surface layer. A model has been proposed to show the influence of structural hierarchy on the electrical surface potential. Structural hierarchy is proposed as a means to further refine the properties of implant surfaces.

• Haugen, Håvard Jostein; Qasim, Syed Saad Bin; Matinlinna, Jukka P; Vallittu, Pekka K. & Nogueira, Liebert Parreiras (2020). Nano-CT as tool for characterization of dental resin composites. Scientific Reports. ISSN 2045-2322. 10. doi: 10.1038/s41598-020-72599-y. Full text in Research Archive Show summary

  Technological advances have made it possible to examine dental resin composites using 3D nanometer resolution. This investigation aims to characterize existing dental nano-hybrid and micro-hybrid resin composites through comparing and contrasting nano-computed tomography (nano-CT) with micro-CT and high-resolution SEM images. Eight commercially available and widely used dental resin composites, 2 micro-hybrid and 6 nano-hybrid were researched. Cured samples were examined and characterized using nano-CT (resolution 450 nm) and compared with micro-CT images (resolution 2 µm). Acquired images were reconstructed and image analysis was carried out to determine porosity and pore morphology. A comprehensive comparison of scanning micrograph images unsurprisingly revealed that the nano-CT images displayed greater detail of the ultrastructure of cured dental resin composites. Filler particle diameters and its volumes were lower when measured using nano-CT, porosity being higher where analysed at higher resolution. There were large variations between the examined materials. Fewer voids were found in Tetric EvoCeram and IPS Empress Direct, the smallest pores being found in Universal XTE and Tetric EvoCeram. Nano-CT was successfully used to investigate the morphology of dental resin composites and showed that micro-CT gives a lower porosity and pore size but overestimates filler particle size. There were large discrepancies between the tested composites. Evidence of porosities and pores within a specimen is a critical finding and it might have a detrimental effect on a material’s clinical performance.

• Kallas, Pawel; Kang, Hua; Valen, Håkon; Haugen, Håvard Jostein; Andersson, Martin & Hulander, Mats (2020). Effect of silica nano-spheres on adhesion of oral bacteria and human fibroblasts. Biomaterial Investigations in Dentistry. 7(1), p. 134–145. doi: 10.1080/26415275.2020.1816175. Full text in Research Archive
• Borie, Manon; Lecloux, Geoffrey; Bosshardt, Dieter D.; Barrantes Bautista, Alejandro; Haugen, Håvard Jostein & Lambert, France [Show all 7 contributors for this article] (2020). Peri-Implant Soft Tissue Integration in Humans – Influence of Materials: A study protocol for a randomised controlled trial and a pilot study results. Contemporary Clinical Trials Communications. ISSN 2451-8654. doi: 10.1016/j.conctc.2020.100643. Full text in Research Archive Show summary

  Background : Recently, there has been a growing interest in mucointegration as the formation of an early and long-standing soft tissue barrier seems essential for both the initial healing and long-term implant survival. Aim: To develop an experimental method to characterize the mucointegration of different transgingival materials (titanium (Ti), polyetheretherketone (PEEK), polymethylmethacrylate (PMMA), zirconia (Zi), polymer infiltrated ceramic network (PICN), cobalt-chrome (Co-Cr), and lithium disilicate (LD)) in a human model. Methods / Design : The study is designed as a multi-part randomized controlled clinical trial. Ninety bone level Straumann implants will randomly receive an experimental, custom-made abutment to allow for the removal of the abutment together with the surrounding soft tissues using a punch biopsy device at 8 weeks of healing (10 per material). The specimens will be further processed for non‐decalcified histology, followed by histomorphometric analysis. The same protocol will be used for additional 90 implants-abutments, but during harvesting, soft tissues will be separated from the abutment and processed for immunohistochemistry in order to study tissue inflammation and vascularization, while the abutments will undergo SEM analysis. Additionally, in vitro analyses, including SEM and profilometry, will be performed in order to characterize surface topography of all experimental materials. Conclusion : The limited number of pilot samples presented herein indicate that the use of custommade abutments in humans is a reproducible method to study peri-implant soft tissue integration. This further intensifies the rationale to compare different abutment materials, used as transgingival components in daily practice, under the same conditions.

• Mengjun, Xue; Sampath, Janani; Gebart, Rachel; Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter & Pfaendtner, Jim [Show all 7 contributors for this article] (2020). Studies of dynamic binding of amino acids to TiO2 nanoparticle surfaces by Solution NMR and Molecular Dynamics Simulations. Langmuir. ISSN 0743-7463. doi: 10.1021/acs.langmuir.0c01256. Full text in Research Archive Show summary

  Adsorption of biomolecules onto material surfaces involves a potentially complex mechanism where molecular species interact to varying degrees with a heterogeneous material surface. Surface adsorption studies by atomic force microscopy (AFM), Sum Frequency Generation (SFG) spectroscopy, and solid state NMR (ssNMR), detect the structures and interactions of biomolecular species that are bound to material surfaces and which, in the absence of a solid liquid interface, do not exchange rapidly between surface-bound forms and free molecular species in bulk solution. Solution NMR has the potential to complement these techniques by detecting and studying transiently bound biomolecules at the liquid-solid interface. Herein we show that dark-state exchange saturation transfer (DEST) NMR experiments on gel-stabilized TiO2 nanoparticle (NP) samples detect several forms of biomolecular adsorption onto titanium (IV) oxide surfaces. Specifically, we use the DEST approach to study the interaction of amino acids arginine (Arg), lysine (Lys), leucine (Leu), alanine (Ala), and aspartic acid (Asp) with TiO2 rutile nanoparticle surfaces. Whereas Leu, Ala, and Asp display only a single weakly interacting form in the presence of TiO2 nanoparticles , Arg and Lys displayed at least two distinct bound forms: a species that is surface bound and retains a degree of reorientational motion, and a second more tightly bound form characterized by broadened DEST profiles upon addition of TiO2 nanoparticles. Molecular Dynamics simulations indicate different surface bound states for both Lys and Arg depending on the degree of TiO2 surface hydroxylation, but only a single bound state for Asp regardless of the degree of surface hydroxylation, in agreement with results obtained from analysis of DEST profiles.

• Haugen, Håvard Jostein; Marovic, Danijela; Par, Matej; Thieu, Minh Khai Le; Reseland, Janne Elin & Johnsen, Gaute Floer (2020). Bulk Fill Composites Have Similar Performance to Conventional Dental Composites. International Journal of Molecular Sciences. ISSN 1422-0067. 21(15). doi: 10.3390/ijms21145136. Full text in Research Archive Show summary

  The aim of the study was to perform comprehensive characterization of two commonly used bulk fill composite materials (SDR Flow (SDR) and Filtek™ Bulk Fill Flowable Restorative (FBF) and one conventional composite material (Tetric EvoCeram; TEC). Eleven parameters were examined: flexural strength (FS), flexural modulus (FM), degree of conversion, depth of cure, polymerisation shrinkage (PS), filler particle morphology, filler mass fraction, Vickers hardness, surface roughness following simulated toothbrush abrasion, monomer elution, and cytotoxic reaction of human gingival fibroblasts, osteoblasts, and cancer cells. The degree of conversion and depth of cure were the highest for SDR, followed by FBF and TEC, but there was no difference in PS between them. FS was higher for bulk fill materials, while their FM and hardness were lower than those of TEC. Surface roughness decreased in the order TEC→SDR→FBF. Bisphenol A-glycidyl methacrylate (BisGMA) and urethane dimethacrylate were found in TEC and FBF eluates, while SDR released BisGMA and triethylene glycol dimethacrylate. Conditioned media accumulated for 24h from FBF and TEC were cytotoxic to primary human osteoblasts. Compared to the conventional composite, the tested bulk fill materials performed equally or better in most of the tests, except for their hardness, elastic modulus, and biocompatibility with osteoblasts.

• Rahmati, Maryam; Frank, Matthias Johannes; Walter, Martin Sebastian; Monjo Cabrer, Marta; Satué, María & Reseland, Janne Elin [Show all 8 contributors for this article] (2020). Osteoimmunomodulatory effects of enamel matrix derivate and strontium coating layers: A short- and long-term in vivo study. ACS Applied Bio Materials (AABM). ISSN 2576-6422. 3, p. 5169–5181. doi: 10.1021/acsabm.0c00608. Full text in Research Archive
• Rahmati, Maryam; Silva, Eduardo A.; Reseland, Janne Elin; Heyward, Catherine Anne & Haugen, Håvard Jostein (2020). Biological responses to physicochemical properties of biomaterial surface. Chemical Society Reviews. ISSN 0306-0012. 49(15), p. 5178–5224. doi: 10.1039/d0cs00103a. Full text in Research Archive
• Rahmati, Maryam; Lyngstadaas, Ståle Petter; Reseland, Janne Elin; Andersbakken, Ingrid; Haugland, Heidi Straume & López-peña, Mónica [Show all 9 contributors for this article] (2020). Coating doxycycline on titanium-based implants: two in vivo studies. Bioactive Materials. ISSN 2452-199X. 5(4), p. 787–797. doi: 10.1016/j.bioactmat.2020.05.007. Full text in Research Archive Show summary

  Regardless of the substantial progress in designing titanium-based dental implants and aseptic techniques, infection remains as the most common complication after implantation surgeries. Although, having a weakened immune system or systematic diseases is not seen as contraindicated for dental implants anymore, controlling the immune system is required to avoid surgical site infections after implantation. These patients have to control the surgical site infections by taking a high daily dose of oral antibiotics after dental implantation. The antibiotics oral administration has many side effects such as gastrointestinal symptoms, skin rashes and thrush. Coating antibiotics on the biomaterials surface could be a promising solution to reduce these disadvantages through locally releasing antibiotics in a controlled manner. The aim of this study was to investigate the effects of doxycycline coating layer on titanium-zirconium alloy surfaces in vitro and in vivo. In our previous studies, we demonstrated the chemical presence of doxycycline layer in vitro. In this study, we examined its physical presence using field emission scanning electron microscope and confocal microscope. We also analyzed its controlled released manner using Nano-Drop UV Vis spectrometer. After in vitro characterization of the coating layer, we evaluated its effects on the implant osseointegration in dogs and rabbits. The histological and histomorphometrical results exhibited no significant difference between doxycycline coated and uncoated groups regarding the implants osseointegration and biocompatibility for dental applications. Therefore, coating a doxycycline layer on TiZr implants could be favorable for reducing or removing the antibiotics oral administration after the implantation surgery.

• Chahal, Aman S; Schweikle, Manuel; Lian, Aina-Mari; Reseland, Janne Elin; Haugen, Håvard Jostein & Tiainen, Hanna (2020). Osteogenic potential of poly(ethylene glycol)-amorphous calcium phosphate composites on human mesenchymal stem cells. Journal of Tissue Engineering. ISSN 2041-7314. 11. doi: 10.1177/2041731420926840. Full text in Research Archive
• Haugen, Håvard Jostein; Basu, Poulami; Sukul, Mousumi; Mano, Joao F. & Reseland, Janne Elin (2020). Injectable biomaterials for Dental Tissue Regeneration. International Journal of Molecular Sciences. ISSN 1422-0067. 21. doi: 10.3390/ijms21103442. Full text in Research Archive Show summary

  Injectable biomaterials scaffolds play a pivotal role for dental tissue regeneration, as such materials are more applicable in the dental field, particularly when compared to pre-formed scaffolds. The defects in maxilla-oral area are normally small, confined and sometimes hard to access. This narrative review described different types of biomaterials for dental tissue regeneration, also discussing the potential use of nanofibres for dental tissues. Various studies suggest that the tissue engineering approaches involving the use of injectable biomaterials have the potential of restoring not only dental tissue function but also their biological purposes

• Sukul, Mousumi; Cama, Giuseppe; Dubruel, Peter; Reseland, Janne Elin & Haugen, Håvard Jostein (2020). Methacrylation increase growth and differentiation of primary human osteoblasts for gelatin hydrogels . Emergent Materials. ISSN 2522-5731. 3, p. 559–566. doi: 10.1007/s42247-020-00101-5. Full text in Research Archive Show summary

  The role of gelatin methacrylate hydrogels with varying degree of methacrylation (69% and 84%) was accessed with FTIR, NMR, microCT and subsequently exposure to human osteoblasts. The cells responded positively to the degree of methacrylation and showed attachment, growth and proliferated on both hydrogels. The cell reacted differently to the degree of methacrylation with higher proliferation on higher substitution; however, cell differentiation behavior was improved for less substitution. The secretion of late osteogenic markers (Osteoprotegerin (OPG), Osteopontin (OPN) and Osteocalcein (OCN)) and angiogenic factor Vascular endothelial growth factor (VEGF) was increased for gelatin methacrylate hydrogels with 69% degree of methacrylation and thus would be the better candidate for future bone regenerative applications amongst the three tested hydrogels

• Rumian, Lucja; Wolf-Brandstetter, Cornelia; Rößler, Sina; Reczyńska, Katarzyna; Tiainen, Hanna & Haugen, Håvard Jostein [Show all 8 contributors for this article] (2020). Sodium alendronate loaded poly(L-lactide-co-glycolide) microparticles immobilized on ceramic scaffolds for local treatment of bone defects. Regenerative Biomaterials. ISSN 2056-3426. p. 1–10. doi: 10.1093/rb/rbaa012. Full text in Research Archive Show summary

  Bone tissue regeneration in critical-size defects is possible after implantation of a three-dimensional scaffold and can be additionally enhanced once the scaffold is enriched with drugs or other factors supporting bone remodelling and healing. Sodium alendronate (Aln), a widely used anti-osteoporosis drug, exhibits strong inhibitory effect on bone resorption performed by osteoclasts. Thus we propose a new approach for the treatment of bone defects in craniofacial region combining biocompatible titanium dioxide (TiO2) scaffolds and poly(L-lactide-co-glycolide) (PLGA) microparticles (MPs) loaded with Aln. The MPs were effectively immobilized on the surface of the scaffolds’ pore walls by human recombinant collagen. Drug release from the scaffolds was characterised by initial burst (24 ± 6% of the drug released within first 24 h) followed by a sustained release phase (on average 5 µg of Aln released per day from day 3 to day 18). In vitro tests showed that Aln in concentrations of 5 µg/mL and 2.5 µg/mL was not cytotoxic for MG-63 osteoblast-like cells (viability between 81 ± 6% to 98 ± 3% of control) but it prevented RANKL-induced formation of osteoclast-like cells from macrophages derived from peripheral blood mononuclear cells (PBMCs), as shown by reduced fusion capability and decreased TRAP 5b activity (56 ± 5% reduction in comparison control after 8 days of culture). Results show that it is feasible to design the scaffolds providing required doses of Aln inhibiting osteoclastogenesis, reducing osteoclast activity, but not affecting osteoblast functions, which may be beneficial in the treatment of critical-size bone tissue defects.

• De-Deus, Gustavo; Simões-Carvalho, Marco; Belladonna, Felipe Goncalves; Versiani, Marcio; Silva, Emmanuel João Nogueira Leal & Cavalcante, Daniele Moreira [Show all 10 contributors for this article] (2020). Creation of well-balanced experimental groups for comparative endodontic laboratorial studies: a new proposal based on micro-CT and in silico methods . International Endodontic Journal. ISSN 0143-2885. doi: 10.1111/iej.13288. Full text in Research Archive Show summary

  Aim To introduce a new method to select anatomically matched teeth using micro-computed tomographic (micro-CT) technology. Methodology Single-rooted mandibular incisors with a single root canal (n = 60) were selected and distributed into three experimental groups according to the method used for matching 10 pairs of teeth in each group. In group 1, the pairs of mandibular incisors were randomly selected from a pool of teeth. In group 2, teeth were paired based on the measurement of canal width 5 mm from the root apex using radiographs taken from buccolingual and mesiodistal directions. In group 3, teeth were scanned (pixel size of 14.25 μm) and pair-matched based on the anatomical aspects of the root canal, named aspect ratio (AR), volume and three-dimensional canal geometry. After allocating the specimens into groups 1 and 2, the teeth were scanned and the canal morphology evaluated as in group 3. A bivariate Pearson’s regression analysis was performed correlating the individual AR values of each pair and the correlation coefficient was used to estimate the strength of the pair-matching process. One-way ANOVA post hoc Tukey tests were applied for pair-wise comparisons at a significance level of 5%. Results The micro-CT method showed 100% of the samples having strong (80%) or very strong (20%) correlations with respect to AR values. Analysis of the radiographic method revealed strong correlation in two pairs (20%), but most of the samples had weak (30%) or neglectable (30%) correlation coefficients. The randomization method resulted in 3 pairs (30%) with very strong correlations, while 50% had weak or neglectable rates. A significant difference in correlation coefficients was observed in the micro-CT method compared to the other groups (p < 0.05), whilst no difference was detected between radiographic and randomized methods (p > 0.05). Eta squared (η 2 ) calculations demonstrated a very high effect size in the micro-CT group for selecting pairs (0.99), and lower effect sizes in the radiographic (0.67) and randomized (0.66) groups. Conclusions Micro-CT method was able to provide better control of the confounding effect that

• Strand, Onur Bülbül; Krockow, Christie Young Ae & Haugen, Håvard Jostein (2020). Hvilke kjeveortopediske metallkomponenter gir pasientreaksjoner og hvilke reaksjoner er registrert? En oversikt over metall-hypersensitivitet innen kjeveortopedien . Den norske tannlegeforenings tidende. ISSN 0029-2303. 130, p. 212–217. Show summary

  Kjeveortopedisk behandling innebærer som oftest behandling med apparaturer bestående av metaller og metallegeringer. Studier har vist at lekkasje av metallioner kan føre til allergiske reaksjoner. Målet med denne artikkelen er å gi en oversikt over forekomst av allergi, kliniske tegn og symptomer, hvilke metallioner som er allergifremkallende og behandlingsalternativer. En allergisk reaksjon skyldes en immunrespons, og de kliniske tegn og symptomer kan manifestere seg både intra- og ekstraoralt. Man bør være oppmerksom på at en allergisk pasient kan ha bare ekstraorale symptomer, selv om apparaturene befinner seg intraoralt. Dette skyldes trolig at mukosa og hud har ulike egenskaper. Nikkel forårsaker mest allergiske reaksjoner sammenlignet med andre metaller i kjeveortopedien og kan utgjøre opptil 70% av noen apparaturer. Til tross for den relativt høye prevalensen av nikkelallergi, er synlige bivirkninger på grunn av metalliske kjeveortopediske apparaturer sjeldne og oppdages hos 0,2 til 0,4 % av pasienter. De fleste allergiske pasienter kan behandles med apparaturer av rustfritt stål. Dersom pasienten fortsatt reagerer, finnes nikkelfrie alternativer. Dette kan i midlertid gi endring av behandlingstid og være lite gunstig i noen kasus

• Haugen, Håvard Jostein; Soltvedt, Brandon Michael; Nguyen, Peter Haitrieu; Rønold, Hans Jacob & Johnsen, Gaute Floer (2020). Discrepancy in alloy composition of imported and non-imported porcelain-fused-to-metal (PFM) crowns produced by Norwegian dental laboratories . Biomaterial Investigations in Dentistry. doi: 10.1080/26415275.2020.1724512. Full text in Research Archive
• Pham, Thi Ngoc Maria Huong; Haugen, Håvard Jostein & Reseland, Janne Elin (2020). Fluoride Modification of Titanium Surfaces Enhance Complement Activation. Materials. ISSN 1996-1944. 13(3). doi: 10.3390/ma13030684. Full text in Research Archive Show summary

  Immediately after dental implant insertion, blood will be in direct contact and interact with the implant surface and activates inflammatory responses and complement cascades within seconds. The aim of the present study was to determine the ability of fluoride-modified titanium surfaces to activate complement cascades using the human buffy coat as model. The buffy coats were exposed to hydrofluoric acid-modified surfaces for a short time and its responses were compared to controls. Identification and quantification of complement cascade biomarkers were conducted using ELISA kits and multianalyte profiling using Luminex. A lower level of C3 at 30 min and increased levels of C4, MIP-4, CRP, and pigment epithelium-derived factor at 360 min were found on modified surfaces as compared to controls. We found no significant differences in the levels of C3a, C5a, C Factor H, α2M, ApoA1, ApoC3, ApoE, Prealbumin, α1AT, and SAP in modified surfaces in the buffy coats. We conclude that titanium surfaces treated with hydrofluoric acid modify the levels of specific biomarkers related to the complement cascade and angiogenesis and, thus, tissue growth, remodeling and repair, as this may play a role in the enhanced clinical performance of fluoride-modified Ti dental implants.

• Rahmati, Maryam; Blaker, Jonathan James; Lyngstadaas, Ståle Petter; Mano, Joao F. & Haugen, Håvard Jostein (2020). Designing multigradient biomaterials for skin regeneration. Materials Today Advances. 5. doi: 10.1016/j.mtadv.2019.100051. Full text in Research Archive 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.

• 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, p. 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.

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• Haugen, Håvard Jostein & Engqvist, Håkan (2021). first editorial for the new journal Scandinavian Journal of Materials Science. Scandinavian Journal of Materials Science. ISSN 2004-2124. 1(1). doi: 10.2340/scandjms.v1.883.
• Rahmati, Maryam; Johannes Frank, Matthias; Martin Walter, Sebastian; Cabrer Monjo, Marta; Satué, Maria & Reseland, Janne Elin [Show all 8 contributors for this article] (2021). Osteo-immune responses to the enamel matrix derivative coating layer on titanium-based implants .
• Rahmati, Maryam; Palombo, David; Vignoletti, Fabio; Javier, Sanz-Esporrin; Haugen, Håvard Jostein & Sanz, Mariano (2021). Tissue healing around PRAMA vs. PREMIUM implants .
• Johannes Frank, Matthias; Walter, Martin Sebastian; Cabrer Monjo, Marta; Satué, Maria; Reseland, Janne E & Ståle Petter, Lyngstadaas [Show all 7 contributors for this article] (2021). Osteo-immune responses to the enamel matrix derivative coating layer on titanium-based implants .
• Haugen, Håvard Jostein & Parreiras Nogueira, Liebert (2021). Novel contrast agent for visualisation of soft tissue with X-ray imaging.
• Haugen, Håvard Jostein; Parreiras Nogueira, Liebert & Sunde, Pia Titterud (2021). Use of novel contrast enhanced agent for tissue engineering.
• Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter; Monjo Cabrer, Marta & Perale, Giuseppe (2021). XENO-HYBRID BONE GRAFT RELEASING MATRIX-DERIVED INTRINSICALLY DISORDERED PROTEINS PROMOTES OSTEOGENIC DIFFERENTIATION OF HMSCS.
• Haugen, Håvard Jostein; Thieu, Minh Khai Le; Sanz-Esporrin, Javier; Sanz Alonso, Mariano & Verket, Anders (2021). GUIDED BONE REGENERATION OF CHRONIC NON-CONTAINED BONE DEFECTS USING A VOLUME STABLE POROUS TIO2 SCAFFOLD: AN EXPERIMENTAL IN VIVO STUDY .
• Linke, Dirk; Økstad, Ole Andreas; Haugen, Håvard Jostein & Winther-Larsen, Hanne Cecilie (2021). The exchange program MISC - Options for internships at the University of Oslo (with descriptions of current projects).
• Rahmati, Maryam; Stoetzel, Sabine; El Khassawna, Thaqif; Wieland, D.C. Florian; Plumhoff, Berit Zeller & Iskhahova, Kamila [Show all 7 contributors for this article] (2021). 2&3D imaging of osteogenesis and macrophage polarization in magnesium-based alloys .
• Rahmati, Maryam; Stoetzel, Sabine; El Khassawna, Thaqif; Wieland, Florian; Iskhahova, Kamila & Plumhoff, Berit Zeller [Show all 7 contributors for this article] (2021). EARLY INFLAMMATORY RESPONSES TO MAGNESIUM-BASED ALLOYS.
• Haugen, Håvard Jostein; Hussain, Badra & Bjørkeng, Astrid Skiftesvik (2021). Er biomaterialer kroppens indre plaster? [Internet]. Universitetsplassen Podcast. Show summary

  Ting går i stykker. Også i kroppen. Men medisinsk forskning har gjort det mulig å erstatte noen ødelagte deler med biomaterialer. I denne podkasten forklarer forskerne Håvard Haugen og Badra Hussein hva biomaterialer er og hvordan de brukes - og ikke minst hvordan de forsker på nye biomaterialer for å lage nytt bein.

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