Ståle Petter Lyngstadaas

• 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), s 1- 24 . doi: 10.3390/molecules26092683 Fulltekst i vitenarkiv. Vis sammendrag

  Chitosan has many useful intrinsic properties (e.g., non-toxicity, antibacterial properties, and biodegradability) and can be processed into high-surface-area nanofiber constructs for a broad range of sustainable research and commercial applications. These nanofibers can be further functionalized with bioactive agents. In the food industry, for example, edible films can be formed from chitosan-based composite fibers filled with nanoparticles, exhibiting excellent antioxidant and antimicrobial properties for a variety of products. Processing ‘pure’ chitosan into nanofibers can be challenging due to its cationic nature and high crystallinity; therefore, chitosan is often modified or blended with other materials to improve its processability and tailor its performance to specific needs. Chitosan can be blended with a variety of natural and synthetic polymers and processed into fibers while maintaining many of its intrinsic properties that are important for textile, cosmeceutical, and biomedical applications. The abundance of amine groups in the chemical structure of chitosan allows for facile modification (e.g., into soluble derivatives) and the binding of negatively charged domains. In particular, high-surface-area chitosan nanofibers are effective in binding negatively charged biomolecules. Recent developments of chitosan-based nanofibers with biological activities for various applications in biomedical, food packaging, and textiles are discussed herein.

• 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 Vis sammendrag

  Objectives To evaluate new lateral bone formation and lateral volume augmentation by guided bone regeneration (GBR) in chronic non‐contained bone defects with the use of a non‐resorbable TiO2‐block. Materials and methods Three buccal bone defects were created in each hemimandible of eight beagle dogs and allowed to heal for eight weeks before treatment by GBR. Each hemimandible was randomly allocated to 4 or 12‐week healing time after GBR and three intervention groups were assigned by block randomization: TiO2 block: TiO2‐scaffold and a collagen membrane, DBBM particles: Deproteinized bovine bone mineral (DBBM) and a collagen membrane, Empty control: Collagen membrane only. Microcomputed tomography (microCT) was used to measure the lateral bone formation and width augmentation. Histological outcomes included descriptive analysis and histomorphometric measurements. Results MicroCT analysis demonstrated increasing new bone formation from four to twelve weeks of healing. The greatest width of mineralized bone was seen in the empty controls, and the largest lateral volume augmentation was observed in the TiO2 block sites. The DBBM particles demonstrated more mineralized bone in the grafted area than the TiO2 blocks, but small amounts and less than the empty control sites. Conclusion The TiO2 blocks rendered the largest lateral volume augmentation but also less new bone formation compared to the DBBM particles. The most new lateral bone formation outward from the bone defect margins was observed in the empty controls, indicating that the presence of either graft material leads to slow appositional bone growth.

• Zhu, Hao; Haugen, Håvard Jostein; Perale, Giuseppe; Reseland, Janne Elin; Nogueira, Liebert Parreiras; Cantalapiedra, Antonio gonzalez; Muñoz, Fernando maria guzon; Permuy Mendaña, Maria; Betge, Felice; Lyngstadaas, Ståle Petter & Xiao, Jun (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 Fulltekst i vitenarkiv. Vis sammendrag

  Bone defects resulting from trauma, surgery, congenital malformations, and other factors are among the most common health problems nowadays. Although current strategies such as autografts and allografts are recognized as the most successful treatments for stimulating bone regeneration, limitations such as graft source and complications still exist. SmartBone® is a xeno-hybrid bone graft (made from bovine bone matrix, poly(L-lactic-co-ε-caprolactone), and gelatin) with a positive clinical record for bone regeneration. In this study, the formulation for designing xeno-hybrid bone grafts using gelatins from different sources (bovine- and porcine-derived gelatin, with bone grafts named SBN and SPK, respectively) was investigated, and the biological responses were evaluated in vitro and in vivo. The results demonstrate that gelatins from both bovine and porcine sources can be loaded onto SmartBone® successfully and safely, withstanding the aggressive manufacturing processes. Different bone cell responses were observed in vitro. SBN was found to enhance osteocalcin secretion while SPK was found to upregulate osteopontin from human osteoblasts. In vivo, both bone grafts promoted osteogenesis, but SPK degraded earlier than SBN. Our findings suggest that SBN and SPK provide different yet comparable solutions for optimizing the bone resorption and regeneration balance. These xeno-hybrid bone grafts possess ideal potential for bone defect repairing.

• Mengjun, Xue; Sampath, Janani; Gebart, Rachel; Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter; Pfaendtner, Jim & Drobny, Gary (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 Fulltekst i vitenarkiv. Vis sammendrag

  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.

• 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: https://doi.org/10.1016/j.mtadv.2019.100051 Fulltekst i vitenarkiv. Vis sammendrag

  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.

• Rahmati, Maryam; Frank, Matthias Johannes; Walter, Martin Sebastian; Monjo Cabrer, Marta; Satué, María; Reseland, Janne Elin; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (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, s 5169- 5181 . doi: 10.1021/acsabm.0c00608 Fulltekst i vitenarkiv. Vis sammendrag

  Over the past few years, surface modification of implant surface has gained substantial attention as a promising solution to avoid the failure of biomaterials after implantation. Although researchers suggest several strategies for surface functionalization of titanium based implants, only few studies have compared the osteoimmunomodulatory effects of ionic nanostructure and biofunctionalization in the same biological model. Enamel matrix derivate (EMD) and strontium are both known for their positive influences on bone cell responses. In this study, we functionalized the titanium-zirconium implant surface with EMD and strontium using an electrochemical cathodic polarization method. Afterwards, we evaluated the osteoimmunomodulatory effects of EMD or strontium coated titanium zirconium implants in the tibia of eight Grey Bastard Chinchillas rabbits. We performed 2&3D micro-CT, wound fluid, histologic, and histomorphometric analyses on bone tissues after 4- and 8-weeks implantation. Although the results could indicate some differences between groups regarding the bone quality, there was no difference in bone amount or volume. EMD stimulated higher ALP activity and lower cytotoxicity in wound fluid, as well as a lower expression of inflammatory markers after 8 weeks indicating its osteoimmunomodulatory effects after implantation. Overall, the results suggested that ionic nanostructure modification and biofunctionalization might be useful in regulating the immune responses to implants.

• Rahmati, Maryam; Lyngstadaas, Ståle Petter; Reseland, Janne Elin; Andersbakken, Ingrid; Haugland, Heidi Straume; López-peña, Mónica; Cantalapiedra, Antonio gonzalez; Muñoz, Fernando maria guzon & Haugen, Håvard Jostein (2020). Coating doxycycline on titanium-based implants: two in vivo studies. Bioactive Materials.  ISSN 2452-199X.  5(4), s 787- 797 . doi: 10.1016/j.bioactmat.2020.05.007 Fulltekst i vitenarkiv. Vis sammendrag

  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.

• Zhu, Hao; Blahnová, Veronika Hefka; Perale, Giuseppe; Xiao, Jun; Betge, Felice; Boniolo, Fabio; Filová, Eva; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (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 Fulltekst i vitenarkiv.
• Giannobile, William V; Berglundh, Tord; Al-Nawas, Bilal; Araujo, Mauricio; Bartold, P Mark; Bouchard, Philippe; Chapple, Iain L.C.; Gruber, Reinhart; Lundberg, Pernilla; Sculean, Anton; Lang, Niklaus P.; Lyngstadaas, Ståle Petter; Kebschull, Moritz; Galindo-Moreno, Pablo; Schwartz, Zvi; Shapira, Lior; Stavropoulos, Andreas & Reseland, Janne Elin (2019). Biological factors involved in alveolar bone regeneration: Consensus report of Working Group 1 of the 15th European Workshop on Periodontology on Bone Regeneration.. Journal of Clinical Periodontology.  ISSN 0303-6979.  46(S21), s 6- 11 . doi: 10.1111/jcpe.13130
• 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 Fulltekst i vitenarkiv. Vis sammendrag

  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.

• Yaddehi Gamage, Thilini Hansamali Gamage; Lengle, Emma; Gunnes, Gjermund; Pullisaar, Helen; Holmgren, Asbjørn; Reseland, Janne Elin; Merckoll, Else; Corti, Stefania; Mizobuchi, Masahiro; Morales, Raul J.; Tsiokas, Leonidas; Tjønnfjord, Geir Erland; Lacruz, Rodrigo S; Lyngstadaas, Ståle Petter; Misceo, Doriana & Frengen, Eirik (2019). STIM1 R304W in mice causes subgingival hair growth and an increased fraction of trabecular bone.. Cell Calcium.  ISSN 0143-4160.  85 . doi: 10.1016/j.ceca.2019.102110
• Córdoba, Alba; Manzanaro-Moreno, Nahuel; Colom, Carme; Rønold, Hans Jacob; Lyngstadaas, Ståle Petter; Monjo, Marta & Ramis, Joana M. (2018). Quercitrin Nanocoated Implant Surfaces Reduce Osteoclast Activity In Vitro and In Vivo. International Journal of Molecular Sciences.  ISSN 1422-0067.  19(11) . doi: 10.3390/ijms19113319 Fulltekst i vitenarkiv.
• Stakkestad, Øystein; Heyward, Catherine Anne; Lyngstadaas, Ståle Petter; Medin, Tirill; Vondrasek, Jiri; Lian, Aina-Mari; Pezeshki, Gita & Reseland, Janne Elin (2018). An ameloblastin C-terminus variant is present in human adipose tissue. Heliyon.  ISSN 2405-8440.  4(12) . doi: 10.1016/j.heliyon.2018.e01075 Fulltekst i vitenarkiv.
• Verket, Anders; Lyngstadaas, Ståle Petter; Tiainen, Hanna; Rønold, Hans Jacob & Wohlfahrt, Johan Caspar (2018). Impact of particulate deproteinized bovine bone mineral and porous titanium granules on early stability and osseointegration of dental implants in narrow marginal circumferential bone defects. International Journal of Oral & Maxillofacial Surgery.  ISSN 0901-5027.  47(8), s 1086- 1094 . doi: 10.1016/j.ijom.2018.02.007 Fulltekst i vitenarkiv.
• Johnsen, Gaute Floer; Thieu, Minh Khai Le; Hussain, Badra; Pamula, Elzbieta; Reseland, Janne Elin; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2017). Own brand label restorative materials - A false bargain?. Journal of Dentistry.  ISSN 0300-5712.  56, s 84- 98 . doi: 10.1016/j.jdent.2016.11.004 Vis sammendrag

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

• Satué, María; Monjo, Marta; Rønold, Hans Jacob; Lyngstadaas, Ståle Petter & Ramis, Joana M. (2017). Titanium implants coated with UV-irradiated vitamin D precursor and vitamin E: in vivo performance and coating stability. Clinical Oral Implants Research.  ISSN 0905-7161.  28(4), s 424- 431 . doi: 10.1111/clr.12815
• Stakkestad, Øystein; Lyngstadaas, Ståle Petter; Thiede, Bernd; Vondrasesek, Jiri; Skålhegg, Bjørn Steen & Reseland, Janne Elin (2017). Phosphorylation Modulates Ameloblastin Self-assembly and Ca2+ Binding. Frontiers in Physiology.  ISSN 1664-042X.  8 . doi: 10.3389/fphys.2017.00531 Fulltekst i vitenarkiv.
• Stakkestad, Øystein; Lyngstadaas, Ståle Petter; Vondrášek, Jiří; Gordeladze, Jan Oxholm & Reseland, Janne Elin (2017). Ameloblastin peptides modulates the osteogenic capacity of human mesenchymal stem cells. Frontiers in Physiology.  ISSN 1664-042X.  8 . doi: 10.3389/fphys.2017.00058 Fulltekst i vitenarkiv.
• Miron, Richard J.; Sculean, Anton; Cochran, David L.; Froum, Stuart; Zucchelli, Giovanni; Nemcovsky, Carlos; Donos, Nikos; Lyngstadaas, Ståle Petter; Deschner, James; Dard, Michel; Stavropoulos, Andreas; Zhang, Yufeng; Trombelli, Leonardo; Kasaj, Adrian; Shirakata, Yoshinori; Cortellini, Pierpaolo; Tonetti, Maurizio; Rasperini, Giulio; Jepsen, Søren & Bosshardt, Dieter D. (2016). Twenty years of enamel matrix derivative: the past, the present and the future. Journal of Clinical Periodontology.  ISSN 0303-6979.  43(8), s 668- 683 . doi: 10.1111/jcpe.12546
• 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
• Villa, Oscar; Wohlfahrt, Johan Caspar; Koldsland, Odd Carsten; Brookes, Steven J; Lyngstadaas, Ståle Petter; Aass, Anne Merete & Reseland, Janne Elin (2016). EMD in periodontal regenerative surgery modulates cytokine profiles: A randomised controlled clinical trial. Scientific Reports.  ISSN 2045-2322.  6, s 1- 9 . doi: 10.1038/srep23060 Fulltekst i vitenarkiv.
• Córdoba, Alba; Satué, María; Gomez-Florit, Manuel; Hierro-Oliva, Margarita; Petzold, Christiane; Lyngstadaas, Ståle Petter; Gonzalez-Martin, Maria Luisa; Monjo, Marta & Ramis, Joana M. (2015). Flavonoid-modified surfaces: Multifunctional bioactive biomaterials with osteopromotive, anti-inflammatory, and anti-fibrotic potential. Advanced Healthcare Materials.  ISSN 2192-2640.  4(4), s 540- 549 . doi: 10.1002/adhm.201400587
• Lyngstadaas, Ståle Petter; Verket, Anders; Pinholt, Else Marie; Mertens, Christian; Haanæs, Hans R; Wall, Gert; Wallström, Mats & Rasmusson, Lars (2015). Titanium granules for augmentation of the maxillary sinus- a multicenter study. Clinical Implant Dentistry and Related Research.  ISSN 1523-0899.  17, s e594- e600 . doi: 10.1111/cid.12291
• Sidaly, Rivan; Landin, Maria Augusta Dos S Silva; Suo, Zhenhe; Snead, Malcom; Lyngstadaas, Ståle Petter & Reseland, Janne Elin (2015). Hypoxia increases the expression of enamel genes and cytokines in an ameloblast-derived cell line. European Journal of Oral Sciences.  ISSN 0909-8836.  123(5), s 335- 340 . doi: 10.1111/eos.12201 Vis sammendrag

  The aim of the study was to investigate the effect of hypoxic conditions on the expression of enamel proteins, and secretion of alkaline phosphatase (ALP), cytokines and interleukins from an ameloblast-derived cell line. The murine ameloblast-derived cells (LS-8) were exposed to 1% oxygen concentration and harvested after 1, 2, 3 and 7 days. The effect of the hypoxic conditions for 24 and 48 h on gene expression, secretion of cytokines and interleukins, and alkaline phosphatase (ALP) activity into the cell medium was calculated relative to the expression and secretion from untreated cells (controls) at each timepoint. Hypoxic exposure increased the expression of the structural enamel matrix proteins; amelogenin (Amel), ameloblastin (Ambn), enamelin (Enam), and the enamel protease matrix metallopeptidase-20 (MMP-20). Expression of Hypoxia-inducible factor 1-alpha (Hif-1a) and secretion of several vascularization factors and pro-inflammatory factors were increased by 24 and 48 hours of hypoxia. ALP activity was reduced after 24 and 48 hours of hypoxia, whereas the LDH level in cell culture medium was higher after exposure to 24 hours compared to 48 hours of hypoxic conditions. In conclusion, hypoxic exposure may disrupt the controlled fine- tuned expression and processing of enamel proteins, and promote the secretion of pro-inflammatory factors.

• Villa, Oscar; Lyngstadaas, Ståle Petter; Monjo, Marta; Satué, María; Rønold, Hans Jacob; Petzold, Christiane & Wohlfahrt, Johan Caspar (2015). Suture materials affect peri-implant bone healing and implant osseointegration. Journal of Oral Science.  ISSN 1343-4934.  57(3), s 219- 227 . doi: 10.2334/josnusd.57.219
• Villa, Oscar; Wohlfahrt, Johan Caspar; Mdala, Ibrahimu; Petzold, Christiane; Reseland, Janne Elin; Snead, Malcolm L. & Lyngstadaas, Ståle Petter (2015). Proline-rich peptide mimic effects of EMD in rat oral mucosal incisional wound healing. Journal of Periodontology.  ISSN 0022-3492.  86(12), s 1386- 1395 . doi: 10.1902/jop.2015.150207
• Villa, Oscar; Brookes, Steven J; Thiede, Bernd; Heijl, Lars; Lyngstadaas, Ståle Petter & Reseland, Janne Elin (2015). Subfractions of enamel matrix derivative differentially influence cytokine secretion from human oral fibroblasts. Journal of Tissue Engineering.  ISSN 2041-7314.  6, s 1- 11 . doi: 10.1177/2041731415575857 Fulltekst i vitenarkiv. Vis sammendrag

  Enamel matrix derivative is used to promote periodontal regeneration during the corrective phase of the treatment of periodontal defects. Our main goal was to analyze the bioactivity of different molecular weight fractions of enamel matrix derivative. Enamel matrix derivative, a complex mixture of proteins, was separated into 13 fractions using size-exclusion chromatography and characterized by sodium dodecyl sulfate–polyacrylamide gel electrophoresis and liquid chromatography–electrospray ionization–tandem mass spectrometry. Human periodontal ligament fibroblasts were treated with either enamel matrix derivative or the different fractions. Proliferation and cytokine secretion to the cell culture medium were measured and compared to untreated cells. The liquid chromatography–electrospray ionization–tandem mass spectrometry analyses revealed that the most abundant peptides were amelogenin and leucine-rich amelogenin peptide related. The fractions containing proteins above 20 kDa induced an increase in vascular endothelial growth factor and interleukin-6 secretion, whereas lower molecular weight fractions enhanced proliferation and secretion of interleukin-8 and monocyte chemoattractant protein-1 and reduced interleukin-4 release. The various molecular components in the enamel matrix derivative formulation might contribute to reported effects on tissue regeneration through their influence on vascularization, the immune response, and chemotaxis.

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

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

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

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

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

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

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

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

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

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

• Gordeladze, Jan Oxholm; Stakkestad, Øystein; Haugen, Sigrid; Reseland, Janne Elin; Syversen, Unni; Johnsen, Gaute Floer; Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter; Møller, Mona & Valtieri, Mauro (2014). Regulatory Loops Consisting of Transcription Factors and MicroRNA Species Determining the Mineralizing Characteristics of Cell Phenotypes - Implications for Bone Engineering and Prevention of Soft Tissue Mineralization, In Daniel Eberli (ed.),  Cells and Biomaterials in Regenerative Medicine.  IntechOpen.  ISBN 978-953-51-1731-5.  Chapter 3.
• Gustumhaugen, Eva; Lönn-Stensrud, Jessica; Scheie, Anne Aamdal; Lyngstadaas, Ståle Petter; Ekfeldt, Anders & Taxt-Lamolle, Sebastien Francis Michel (2014). Effect of chemical and mechanical debridement techniques on bacterial re-growth on rough titanium surfaces: an in vitro study. Clinical Oral Implants Research.  ISSN 0905-7161.  25(6), s 707- 713 . doi: 10.1111/clr.12130 Vis sammendrag

  Objective The aim of this in vitro study was to compare the effect of combined chemical and mechanical debridement of titanium (Ti) surfaces inoculated with Staphylococcus epidermidis, compared with the effect of chemical debridement alone. Material and Methods Different Ti surfaces were characterized with respect to roughness and subsequently inoculated with S. epidermidis. NaCl (0.9 vol.%), EDTA (12 vol.%), H2O2 (3 vol.%) or H2O2 + TiO2 nanoparticles served as chemical debridement agents, while TiBrush™ was used as the mechanical debridement tool. Safranin staining assessed biomass still attached to surfaces after debridement. Biofilm viability was assessed after re-incubation of the debrided samples. SEM analysis was performed before and after the cleaning process. Results Surface average roughness (Sa) of the samples was measured at 2.22 ± 0.19 μm for group A, 0.19 ± 0.02 μm for group B, and 1.99 ± 0.10 μm for group C. When chemical debridement agents were used alone, H2O2-containing products were most efficient in reducing the biomass load. The surface roughness did not affect the outcome of chemical debridement. However, when combining chemical and mechanical debridement, a further reduction of biofilm load and viability was observed with best effect on the smoothest surface. Conclusions Combining H2O2-containing chemical agents with mechanical debridement (TiBrush™) provided best reduction in biofilm mass and re-growth, when studied in vitro.

• Ignjatović, Nenad L.; Ninkov, Peter; Sabetrasekh, Roya; Lyngstadaas, Ståle Petter & Uskoković, Dragan P. (2014). In vitro evaluation of a multifunctional nano drug delivery system based on tigecycline-loaded calcium-phosphate/ poly-DL-lactide-co-glycolide. Bio-medical materials and engineering.  ISSN 0959-2989.  24(4), s 1647- 1658 . doi: 10.3233/BME-140978
• Reikerås, Olav; Borgen, Pål; Reseland, Janne Elin & Lyngstadaas, Ståle Petter (2014). Changes in serum cytokines in response to musculoskeletal surgical trauma. BMC Research Notes.  ISSN 1756-0500.  7(1) . doi: 10.1186/1756-0500-7-128
• Riksen, Elisabeth Aurstad; Landin, Maria Augusta Dos S Silva; Reppe, Sjur; Nakamura, Yoikio; Lyngstadaas, Ståle Petter & Reseland, Janne Elin (2014). Enamel Matrix Derivative Promote Primary Human Pulp Cell Differentiation and Mineralization. International Journal of Molecular Sciences.  ISSN 1422-0067.  15(5), s 7731- 7749 . doi: 10.3390/ijms15057731 Fulltekst i vitenarkiv.
• Verket, Anders; Lyngstadaas, Ståle Petter; Rønold, Hans Jacob & Wohlfahrt, Johan Caspar (2014). Osseointegration of dental implants in extraction sockets preserved with porous titanium granules - an experimental study. Clinical Oral Implants Research.  ISSN 0905-7161.  25(2), s E100- E108 . doi: 10.1111/clr.12070
• Walter, Martin Sebastian; Frank, Matthias Johannes; Rubert, Marina; Monjo, Marta; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2014). Simvastatin-activated implant surface promotes osteoblast differentiation in vitro. Journal of Biomaterials Applications.  ISSN 0885-3282.  28(6), s 897- 908 . doi: 10.1177/0885328213486364 Vis sammendrag

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

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

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

• Wohlfahrt, Johan Caspar; Aass, Anne Merete; Granfeldt, Finn; Lyngstadaas, Ståle Petter & Reseland, Janne Elin (2014). Sulcus fluid bone marker levels and the outcome of surgical treatment of peri-implantitis. Journal of Clinical Periodontology.  ISSN 0303-6979.  41(4), s 424- 431 . doi: 10.1111/jcpe.12229
• Xing, Rui; Salou, Laëtitia; Taxt-Lamolle, Sebastien Francis Michel; Reseland, Janne Elin; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2014). Surface Hydride on Titanium by Cathodic Polarization Promotes Human Gingival Fibroblast Growth. Journal of Biomedical Materials Research. Part A.  ISSN 1549-3296.  102(5), s 1389- 1398 . doi: 10.1002/jbm.a.34819 Vis sammendrag

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

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

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

• Frank, Matthias Johannes; Walter, Martin Sebastian; Tiainen, Hanna; Rubert, Marina; Monjo, Marta; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2013). Coating of metal implant materials with strontium. Journal of materials science. Materials in medicine.  ISSN 0957-4530.  24(11), s 2537- 2548 . doi: 10.1007/s10856-013-5007-1
• Gordeladze, Jan Oxholm; Reseland, Janne Elin; Karlsen, Tommy Aleksander; Jakobsen, Rune Bruhn; Stunes, Astrid Kamilla; Syversen, Unni; Engebretsen, Lars; Lyngstadaas, Ståle Petter & Jorgensen, Christian (2013). Engineering of Inflammation-Resistant Osteochondral Cells, In Jose A. Andrades (ed.),  Regenerative Medicine and Tissue Engineering.  IntechOpen.  ISBN 978-953-51-1108-5.  20.
• Haugen, Håvard Jostein; Monjo Cabrer, Marta; Rubert, Marina; Verket, Anders; Lyngstadaas, Ståle Petter; Ellingsen, Jan Eirik; Rønold, Hans Jacob & Wohlfahrt, Johan Caspar (2013). Porous Ceramic Titanium Dioxide Scaffolds Promote Bone Formation in Rabbit Peri-Implant Cortical Defect Model. Acta Biomaterialia.  ISSN 1742-7061.  9(2), s 5390- 5399 . doi: 10.1016/j.actbio.2012.09.009 Vis sammendrag

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

• Lacruz, Rodrigo S; Brookes, Steven J; Wen, Xin; Jimenez, Jaime M; Vikman, Susanna; Hu, Ping; White, Shane N; Lyngstadaas, Ståle Petter; Okamoto, Curtis T; Smith, Charles E & Paine, Michael L (2013). Adaptor protein complex 2-mediated, clathrin-dependent endocytosis, and related gene activities, are a prominent feature during maturation stage amelogenesis. Journal of Bone and Mineral Research.  ISSN 0884-0431.  28(3), s 672- 687 . doi: 10.1002/jbmr.1779
• Monjo Cabrer, Marta; Ramis, Joana M.; Rønold, Hans Jacob; Taxt-Lamolle, Sebastien Francis Michel; Ellingsen, Jan Eirik & Lyngstadaas, Ståle Petter (2013). Correlation between molecular signals and bone bonding to titanium implants. Clinical Oral Implants Research.  ISSN 0905-7161.  24(9), s 1035- 1043 . doi: 10.1111/j.1600-0501.2012.02496.x
• Petzold, Christiane; Monjo, Marta; Rubert, Marina; Reinholt, Finn P.; Gomez-Florit, Manuel; Ramis, Joana Maria; Ellingsen, Jan Eirik & Lyngstadaas, Ståle Petter (2013). Effect of Proline-Rich Synthetic Peptide-Coated Titanium Implants on Bone Healing in a Rabbit Model. International Journal of Oral & Maxillofacial Implants.  ISSN 0882-2786.  28(6), s E547- E555 . doi: 10.11607/jomi.te35
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Reseland, Janne Elin & Østrup, Esben (2013). Enhanced in vitro osteoblast differentiation on TiO2 scaffold coated with alginate hydrogel containing simvastatin. Journal of Tissue Engineering.  ISSN 2041-7314.  4, s 1- 13 . doi: 10.1177/2041731413515670 Fulltekst i vitenarkiv. Vis sammendrag

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

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

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

• Verket, Anders; Lyngstadaas, Ståle Petter; Rasmusson, Lars; Haanæs, Hans R; Wallstrøm, M.; Wall, Gert & Wohlfahrt, Johan Caspar (2013). Maxillary Sinus Augmentation with Porous Titanium Granules: A Microcomputed Tomography and Histologic Evaluation of Human Biopsy Specimens. International Journal of Oral & Maxillofacial Implants.  ISSN 0882-2786.  28(3), s 721- 728 . doi: 10.11607/jomi.2853 Vis sammendrag

  PURPOSE: The aim of this study was to assess bone ingrowth into porous titanium granules used for maxillary sinus augmentation. MATERIALS AND METHODS: Eighteen biopsy specimens from 17 patients participating in a clinical trial on sinus augmentation using porous titanium granules (PTG) were received in the laboratory. The specimens (trephine cores of 4.5 mm) were obtained 6 months after PTG placement. After being embedded in methacrylate, the samples were scanned in a microcomputed tomography (micro-CT) scanner. Specimens were then cut along the long axis and central slices were ground to 70 μm before staining with hematoxylin and eosin. RESULTS: The micro-CT analysis demonstrated an average bone fill of 19% (standard deviation [SD] 5.8%), whereas the graft material occupied 22.7% (SD 4.7%). The volume of newly formed bone decreased with the distance from the residual bone of the sinus floor. Two-dimensional histomorphometric analysis demonstrated a mean area of new bone of 16.1% (SD 9.4%). The PTG alone occupied 25.9% of the total mean area (SD 6.1%). The newly formed bone consisted mainly of woven bone growing in close contact with the granules and bridging the intergranular space. The remaining area was occupied predominantly by nonmineralized connective tissue. There were no signs of inflammation in any of the biopsy specimens. CONCLUSIONS: After 6 months, new bone had formed at a similar rate and quality as has been reported for other well-recognized bone graft substitutes. The new bone formed in close contact with the PTG, suggesting that the material is osteoconductive.

• Walter, Martin Sebastian; Frank, Matthias Johannes; Sunding, Martin Fleissner; Gomez-Florit, Manuel; Monjo Cabrer, Marta; Bucko, Miroslaw M.; Pamula, Elzbieta; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2013). Increased reactivity and in vitro cell response of titanium based implant surfaces after anodic oxidation. Journal of materials science. Materials in medicine.  ISSN 0957-4530.  24(12), s 2761- 2773 . doi: 10.1007/s10856-013-5020-4 Vis sammendrag

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

• Walter, Martin Sebastian; Frank, Matthias Johannes; Sunding, Martin Fleissner; Gomez-Florit, Manuel; Monjo, Marta; Bucko, Miroslaw M.; Pamula, Elzbieta; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2013). Increased reactivity and in vitro cell response of titanium based implant surfaces after anodic oxidation. Journal of materials science. Materials in medicine.  ISSN 0957-4530.  24(12), s 2761- 2773 . doi: 10.1007/s10856-013-5020-4 Vis sammendrag

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

• Almqvist, Sofia; Werthen, Maria; Lyngstadaas, Ståle Petter; Gretzer, Christina & Thomsen, Peter (2012). Amelogenins modulate cytokine expression in LPS-challenged cultured human macrophages. Cytokine.  ISSN 1043-4666.  58(2), s 274- 279 . doi: 10.1016/j.cyto.2012.02.001
• Bashara, Haitham; Wohlfahrt, Johan Caspar; Polyzois, Ioannis; Lyngstadaas, Ståle Petter; Renvert, Stefan & Claffey, Noel (2012). The effect of permanent grafting materials on the preservation of the buccal bone plate after tooth extraction: an experimental study in the dog. Clinical Oral Implants Research.  ISSN 0905-7161.  23(8), s 911- 917 . doi: 10.1111/j.1600-0501.2011.02240.x
• Frank, Matthias Johannes; Walter, Martin Sebastian; Lyngstadaas, Ståle Petter; Wintermantel, Erich & Haugen, Håvard Jostein (2012). Hydrogen content in titanium and a titanium-zirconium alloy after acid etching. Materials Science and Engineering C: Materials for Biological Applications.  ISSN 0928-4931. . doi: 10.1016/j.msec.2012.12.027
• Gomez-Florit, Manuel; Rubert, Marina; Ramis, Joana Maria; Haugen, Håvard Jostein; Tiainen, Hanna; Lyngstadaas, Ståle Petter & Monjo, Marta (2012). TiO2 Scaffolds Sustain Differentiation of MC3T3-E1 Cells. Journal of Biomaterials and Tissue Engineering (JBT).  ISSN 2157-9083.  2(4), s 336- 344 . doi: 10.1166/jbt.2012.1055
• Kolseth, Ingrid Moss; Førland, Dag T.; Risøe, Petter Kirkeby; Kjeldsen, Signe Flood; Ågren, Joanna; Reseland, Janne Elin; Lyngstadaas, Ståle Petter; Johnson, Egil & Dahle, Maria Krudtaa (2012). Human monocyte responses to lipopolysaccharide and 9-cis retinoic acid after laparoscopic surgery for colon cancer. Scandinavian Journal of Clinical and Laboratory Investigation.  ISSN 0036-5513.  72(8), s 593- 601 . doi: 10.3109/00365513.2012.721520
• Kolseth, Ingrid Moss; Ågren, Joanna; Gjerstad, Vibeke Sundvold; Lyngstadaas, Ståle Petter; Wang, Jacob Edward & Dahle, Maria Krudtaa (2012). 9-cis Retinoic Acid Inhibits Inflammatory Responses of Adherent Monocytes and Increases Their Ability to Induce Classical Monocyte Migration. Journal of Innate Immunity.  ISSN 1662-811X.  4(2), s 176- 186 . doi: 10.1159/000332375
• Monjo, Marta; Petzold, Christiane; Ramis, Joana Maria; Lyngstadaas, Ståle Petter & Ellingsen, Jan Eirik (2012). In vitro osteogenic properties of two dental implant surfaces. International Journal of Biomaterials.  ISSN 1687-8787. . doi: 10.1155/2012/181024
• Petzold, Christiane; Gomez-Florit, Manuel; Lyngstadaas, Ståle Petter & Monjo, Marta (2012). EPA covalently bound to smooth titanium surfaces decreases viability and biofilm formation of Staphylococcus epidermidis in vitro. Journal of Orthopaedic Research.  ISSN 0736-0266.  30(9), s 1384- 1390 . doi: 10.1002/jor.22089
• Petzold, Christiane; Monjo, M; Rubert, M; Reinholt, Finn P; Gomez-Florit, Manuel; Ramis, Joana Maria; Ellingsen, Jan Eirik & Lyngstadaas, Ståle Petter (2012). Effect of Proline-Rich Synthetic Peptide-Coated Titanium Implants on Bone Healing in a Rabbit Model. Oral & Craniofacial Tissue Engineering.  ISSN 2158-3722.  2(1), s 35- 43
• Ramis, Joana M.; Taxt-Lamolle, Sebastien Francis Michel; Lyngstadaas, Ståle Petter; Reseland, Janne Elin; Ellingsen, Jan Eirik & Monjo, Marta (2012). Identification of Early Response Genes to Roughness and Fluoride Modification of Titanium Implants in Human Osteoblasts. Implant Dentistry.  ISSN 1056-6163.  21(2), s 141- 149 . doi: 10.1097/ID.0b013e31824a06b4
• Ramis, Joana Maria; Rubert, Marina; Vondrášek, Jiří; Gaya, Antoni; Lyngstadaas, Ståle Petter & Monjo, Marta (2012). Effect of Enamel Matrix Derivative and of Proline-Rich Synthetic Peptides on the Differentiation of Human Mesenchymal Stem Cells Toward the Osteogenic Lineage. Tissue Engineering.  ISSN 1076-3279.  18(11-12), s 1253- 1263 . doi: 10.1089/ten.tea.2011.0404
• Rubert, M; Monjo, Marta; Lyngstadaas, Ståle Petter & Ramis, J M (2012). Effect of alginate hydrogel containing polyproline-rich peptides on osteoblast differentiation. Biomedical Materials.  ISSN 1748-6041.  7(5) . doi: 10.1088/1748-6041/7/5/055003
• Stanisic, Milo; Aasen, Ansgar Oddne; Pripp, Are Hugo; Lindegaard, Karl-Fredrik; Ramm-Pettersen, Jon-Terje; Lyngstadaas, Ståle Petter; Ivanovic, Jugoslav; Konglund, Ane; Ilstad, Eivind; Sandell, Tiril; Ellingsen, Omar & Sæhle, Terje (2012). Local and systemic pro-inflammatory and anti-inflammatory cytokine patterns in patients with chronic subdural hematoma: a prospective study. Inflammation Research.  ISSN 1023-3830.  61(8), s 845- 852 . doi: 10.1007/s00011-012-0476-0
• Stanisic, Milo; Lyngstadaas, Ståle Petter; Pripp, Are Hugo; Aasen, Ansgar Oddne; Lindegaard, Karl-Fredrik; Ivanovic, Jugoslav; Ilstad, Eivind; Konglund, Ane; Sandell, Tiril; Ellingsen, Theodor Omar Chammas & Sæhle, Terje (2012). Chemokines as markers of local inflammation and angiogenesis in patients with chronic subdural hematoma: a prospective study. Acta Neurochirurgica.  ISSN 0001-6268.  154(1), s 113- 120 . doi: 10.1007/s00701-011-1203-2
• Tiainen, Hanna; Verket, Anders; Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter & Wohlfahrt, Johan Caspar (2012). Dimensional ridge preservation with a novel highly porous TiO2 scaffold: an experimental study in minipigs. International Journal of Biomaterials.  ISSN 1687-8787. . doi: 10.1155/2012/851264

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• 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.
• Grytten, Jostein Ivar; Aass, Anne Merete; Lyngstadaas, Ståle Petter; Brodin, Pål; Ellingsen, Jan Eirik & Barkvoll, Pål (2015). Kompetansesentrenes forsvarsskrift - en korreksjon til deres realitetsorientering. Den norske tannlegeforenings tidende.  ISSN 0029-2303.  125(5), s 459- 462
• Longela, Simon Makusudi; Haugen, Håvard Jostein; Tiainen, Hanna; Lyngstadaas, Ståle Petter & Reseland, Janne Elin (2015). Biomolecular coating of nickel-titanium memory shape metals. European Cells and Materials.  ISSN 1473-2262.  29, s 32
• Villa, Oscar; Wohlfahrt, Johan Caspar; Mdala, Ibrahimu; Petzold, Christiane; Reseland, Janne Elin; Snead, Malcolm L. & Lyngstadaas, Ståle Petter (2015). Proline-rich peptides accelerate oral mucosal wound healing.
• Geissler, Sebastian; Frank, Matthias Johannes; Walter, Martin Sebastian; Tiainen, Hanna; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2014). Coating of metal implant materials with strontium.
• Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter & Vogt, Yngve (2014, 03. mars). Redder løse tenner og kreftskadde kjever. [Fagblad].  Apollon.
• Walter, Martin Sebastian; Frank, Matthias Johannes; Satué, María; Monjo, Marta; Rønold, Hans Jacob; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2014). Erratum; Bioactive implant surface with electrochemically bound doxycycline promotes bone formation markers in vitro and in vivo (Dental Materials (2014) 30:2 (200-214)). Dental Materials.  ISSN 0109-5641.  30(4), s 463 . doi: 10.1016/j.dental.2014.01.015?
• Wohlfahrt, Johan Caspar; Lyngstadaas, Ståle Petter; Aass, Anne Merete & Koldsland, Odd Carsten (2014). Implant Maintenance with a Chitosan Brush –A Randomized Clinical Trial.
• Tiainen, Hanna; Wiedmer, David; Wohlfahrt, Johan Caspar; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2013). Highly porous ceramic TiO2 scaffolds for bone repair.
• Tiainen, Hanna; Wiedmer, David; Wohlfahrt, Johan Caspar; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2013). Highly porous ceramic titanium dioxide scaffolds for bone repair.
• Córdoba, Alba; Satué, María; Petzold, Christiane; Hierro, Margarita; Gonzáles-Martín, María-Luisa; Lyngstadaas, Ståle Petter; Monjo, Marta & Ramis, Joana Maria (2013). Bioactive titanium surfaces functionalized with flavonoids for improving dental implant osseointegration.
• Haugen, Håvard Jostein & Lyngstadaas, Ståle Petter (2013). Like sterke som originalen. Den norske tannlegeforenings tidende.  ISSN 0029-2303.  123, s 730- 731 Vis sammendrag

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

• Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter & Verket, Anders (2013). Tannleger uten framtidsskrekk. Forskning.no.  ISSN 1891-635X.
• Müller, Benjamin; Wengenroth, Jonas; Tiainen, Hanna; Haugen, Håvard Jostein & Lyngstadaas, Ståle Petter (2013). Bone-structural mimicry of TiO2 scaffolds for regeneration of alveolar defects.
• Müller, Benjamin; Wengenroth, Jonas; Tiainen, Hanna; Haugen, Håvard Jostein & Lyngstadaas, Ståle Petter (2013). TiO2 Scaffolds with Cortical Bone Imitation for Enhanced Alveolar Bone Defect Healing.
• Müller, Benjamin; Wengenroth, Jonas; Tiainen, Hanna; Haugen, Håvard Jostein & Lyngstadaas, Ståle Petter (2013). TiO2 scaffolds with pore size gradient to avoid soft tissue ingrowth in alveolar defects.
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Reseland, Janne Elin & Østrup, Esben (2013). Coating titanium dioxide scaffold with simvastatin in alginate promote osteoblast differentiation in vitro.
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Reseland, Janne Elin & Østrup, Esben (2013). Enhanced in vitro bone differentiation on TiO₂ scaffold coated with simvastatin.
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Reseland, Janne Elin & Østrup, Esben (2013). Local delivery of simvastatin enhances bone differentiation on porous titanium dioxide scaffold.
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Reseland, Janne Elin & Østrup, Esben (2013). Local delivery of simvastatin on titanium dioxide scaffolds; a tissue engineering model.
• Villa, Oscar; Brookes, Steven J; Heijl, Lars; Lyngstadaas, Ståle Petter & Reseland, Janne Elin (2013). Subfractions of enamel matrix derivative differentially influence cytokine secretion from human oral fibroblasts.
• Villa, Oscar; Lyngstadaas, Ståle Petter; Monjo, Marta; Rønold, Hans Jacob; Petzold, Christiane & Wohlfahrt, Johan Caspar (2013). The influence of suture remnants on peri-implant bone healing - A pilot animal experimental study. Vis sammendrag

  Background: Suture remnants may potentially induce an inflammation and influence peri-implant osseous healing. It might thus be preferable to use a resorbable suture material in order to avoid soft and hard tissue complications. Aim: To evaluate the influence of remnants of suture filaments on osseointegration in a rabbit tibial model. Material and methods: In this pilot animal experimental study calibrated defects were prepared in the tibia of 5 chinchilla rabbits. Four sites were prepared in each animal and randomized to one of the three groups. Test filaments of nylon and chitosan were placed at the prepared implant sites before implant placement. A sham site was used as control. A coin-shaped machined titanium implant covered with a teflon cap and a preshaped maxillofacial bone plate were seated over the prepared cortical bone. After a healing period of 4 weeks, rabbits were euthanized and the tibial bone with the implants was exposed and removed. The implants were subjected to a pull-out test procedure. Wound fluid was collected with filter papers for the analyses of lactate dehydrogenase activity, alkaline phosphatase activity and total protein. Total-RNA was isolated from the peri-implant bone tissue. Real time PCR was performed for the following target genes: vacuolar type proton ATPase, insulin like growth factor-1, bone morphogenetic protein-2 , collagen-1, interleukin-10, interleukin-6, osteocalcin, calcitonin receptor, tartrate-resistant acid phosphatase and tumor necrosis factor-α. A one-way analysis of variance was used to detect differences across groups with the significance level set at 0.05. Results: When comparing the data across the three groups no statistically significant differences were found. There was, however, a trend towards a reduced pull-out force for the nylon group (Nylon: 23.0 ± 12.8; Chitosan: 33.9 ± 11.3; Sham 33.6 ± 24.0). Similarly, the resorption bone marker vacuolar type proton ATPase was increased in the nylon group compared to the sham and chitosan groups. The chitosan group showed lower ALP activity and lower expression of osteocalcin compared to the nylon group. Conclusions and clinical implications: In this closed surgical model, peri-implant bone healing was only marginally affected by the different materials tested. There was, however, a tendency toward better osseointegration and less expression of bone resorption markers in the sham and chitosan groups as compared to the nylon group. The number of animals was low in this pilot study and further research is warranted to explore this issue. The influence of suture remnants on peri-implant bone healing - A pilot animal experimental study.

• Walter, Martin Sebastian; Frank, Matthias Johannes; Rubert, Marina; Monjo, Marta; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2013). Simvastatin bound to grit blasted and acid etched titanium zirconium by anodic oxidation increased alkaline phosphatase, collagen type I and osteocalcin expression in vitro.
• Frank, Matthias Johannes; Walter, Martin Sebastian; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2012). Hydride layer created by hot acid etching suppressed hydride formation by cathodic reduction on titanium based implant surfaces.
• Frank, Matthias Johannes; Walter, Martin Sebastian; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2012). Hydride layer created by hot acid etching suppresses hydride formation by cathodic reduction on titanium based implant surfaces.
• Gustumhaugen, Eva; Lönn-Stensrud, Jessica; Scheie, Anne Aamdal; Lyngstadaas, Ståle Petter & Taxt-Lamolle, Sebastien Francis Michel (2012). Chemical and Mechanical Debridement of Rough Titanium Surfaces in vitro.
• Haugen, Håvard Jostein; Monjo Cabrer, Marta; Lyngstadaas, Ståle Petter & Wohlfahrt, Johan Caspar (2012). Ultra-Porous Ceramic Titanium Dioxide Bone grafts Promote Bone Healing in Rabbit Peri-Implant Cortical Defect Model.
• Petzold, Christiane; Gomez-Florit, Manuel; Lyngstadaas, Ståle Petter & Monjo, Marta (2012). Effect of Fatty Acid Coated Titanium on Viability of Staphylococcus Epidermidis and Membrane-Surface Interactions and Mineralization of MC3T3-E1 Cells.
• Petzold, Christiane; Lyngstadaas, Ståle Petter & Monjo, Marta (2012). Growth and viability of S. epidermidis on UV irradiated and fatty acid-coated smooth titanium surfaces.
• Pullisaar, Helen; Reseland, Janne Elin; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2012). Loading and release of simvastatin from titanium dioxide scaffolds.
• Tiainen, Hanna; Wohlfahrt, Johan Caspar; Verket, Anders; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2012). Bone formation in TiO2 bone scaffolds in extraction sockets of minipigs. Bone.  ISSN 8756-3282.  50, s S115- S115 . doi: 10.1016/j.bone.2012.02.354

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