Ståle Petter Lyngstadaas

• Saiz, Augustine Mark; Jamous, Reem; Stötzel, Sabine; Rahmati, Maryam; Holmboe, Leonard Volrath & Johnson, Soren [Show all 16 contributors for this article] (2026). Limited Added Effect of Proline‐Rich P6 Peptide to Cross‐Linked Hyaluronic Acid After Partial Lateral Meniscectomy in Sheep. Smart Medicine. ISSN 2751-1863. 5(4). doi: 10.1002/smmd.70048. Full text in Research Archive Show summary

  This study evaluates whether a proline‐rich P6 peptide provides added benefit to a cross‐linked hyaluronic acid (HA) hydrogel after partial lateral meniscectomy‐associated osteoarthritis‐like change in sheep. The corrected four‐group framework includes Intact no‐surgery/no‐injection reference knees ( n  = 7) and 16 surgically injured knees from eight sheep assigned to Mnx (meniscectomy only, n  = 4), Mnx + HA ( n  = 6), or Mnx + HA + P6 ( n  = 6). Mnx + HA and Mnx + HA + P6 knees received intra‐articular injections at Weeks 0, 1, 2, and 4. Osteochondral tissues were evaluated at Week 12 by microCT, H&E scoring, and histochemical/immunohistochemical image analysis. Endpoint‐specific animal‐ or knee‐level models were used, with sheep identity included as a random effect when estimable. HA‐based treatment was associated with favorable trabecular microCT patterns after meniscectomy. However, the primary Mnx + HA + P6 versus Mnx + HA contrast was not significant for percent trabecular bone volume/BV/TV (+1.52 percentage points; 95% CI −2.22 to 5.26; p  = 0.427). Histology and IHC/histochemical findings showed selected exploratory tissue‐pattern signals, including collagen‐associated matrix staining, but did not establish consistent peptide‐specific superiority. These findings support cross‐linked HA as an intra‐articular biomaterial platform while defining requirements for confirmatory HA‐peptide hydrogel studies.

• Jamous, Reem; Nysæther, Ingvild; Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter; Fredriksson, Malin Vestin & Ellingsen, Jan Eirik [Show all 7 contributors for this article] (2026). Multi-Scale Assessment of Scaffold-Guided Regeneration in Human Extraction Sockets Using an Ultra-Porous TiO₂ Biomaterial. Acta Biomaterialia. ISSN 1742-7061. doi: 10.1016/j.actbio.2026.08.041. Full text in Research Archive Show summary

  Ultra-porous TiO₂ scaffolds are architected non-degradable ceramic graft substitutes, but human evidence relating their structural integration to local tissue maturation remains limited. This exploratory study assessed scaffold-associated healing in a prospective clinical cohort registered at ClinicalTrials.gov (NCT06269497; 10 patients, 11 treated sites). Cone-beam computed tomography (CBCT)-based segmentation at baseline and follow-up was used to quantify changes in bone volume, radiographic low-density/non-mineralized volume, and radiographically detectable scaffold volume. Eleven scaffold-associated specimens were examined using non-decalcified histology, histomorphometry, and immunohistochemistry; nine were retrieved at approximately 6 months, one at 4 months, and one at 9 months. CBCT showed within-site increases in bone and total tissue volume and a reduction in radiographically detectable scaffold volume. Histology showed extensive pore colonization by osteoid-rich tissue, localized mineralization, and limited residual cartilage, consistent with ongoing but incomplete matrix maturation. Normalized RunX2 showed a positive exploratory association with absolute bone volume change, whereas associations with osteocalcin were uncertain and endpoint-dependent. CD206/CD68 and the vessel-to-osteoid ratio were more closely associated with low-density/non-mineralized volume outcomes than with bone-volume change. Osteoclast-associated variables were evaluable in only four sites and were interpreted descriptively. These findings are exploratory and do not establish causality or comparative efficacy, but they characterize tissue-scaffold interactions during human extraction-socket healing.

• Lauretis, Angela De; Santacroce, Marco; Wang, Qiang; Ramirez, Manuel; Ma, Qianli & Lyngstadaas, Ståle Petter [Show all 9 contributors for this article] (2026). Combined Chemical and Mechanical Debridement Enhances Salivary Protein Removal from Titanium while Maintaining Biological Properties. ACS Biomaterials Science and Engineering. doi: 10.1021/acsbiomaterials.5c01973. Full text in Research Archive Show summary

  Effective decontamination of dental implants is essential for managing peri-implant diseases, yet its impact on the salivary pellicle and cell response remains unclear. As the pellicle mediates bacterial and host cell interactions, investigating how decontamination alters its composition is key to understanding the effects on biological outcomes. Accordingly, we examined how a Poloxamer 407 (P407) hydrogel, a P407 + hydrogen peroxide (H2O2) hydrogel, a titanium brush, and their combinations influence the adsorbed salivary proteins and cell adhesion on OsseoSpeed-like titanium surfaces. Surfaces with salivary proteins were treated with different decontamination methods and re-exposed to saliva. Protein quantity was measured using the BCA assay, while the proteomic composition and molecular functions of the adsorbed proteins were determined by liquid chromatography-mass spectrometry and gene ontology analysis. Human bone marrow mesenchymal stem cell (hBMMSC) adhesion was assessed on the surfaces, and cytotoxicity was evaluated using an LDH assay. Protein-coated and protein-free surfaces served as controls. Although protein levels were consistent across groups after either decontamination or recontamination, each treatment produced a different proteomic profile. Mechanical decontamination, alone or combined with chemicals, enhanced protein removal efficiency. Combined treatments yielded reduced protein diversity following recontamination and enriched adhesion-related proteins. None of the treatments compromised hBMMSC adhesion nor made the surface cytotoxic. Decontamination methods selectively modify the proteomic profile. Combined chemical and mechanical decontamination promotes the removal of salivary proteins and limits their readsorption while preserving cytocompatibility, supporting their relevance to peri-implant health.

• Reese, Jan-Ole; Lund, Ingrid Maria Castro; Haugen, Håvard Jostein; Saragliadis, Athanasios; Lyngstadaas, Ståle Petter & Linke, Dirk (2026). A dual-loop chemostat to investigate multi-species biofilms on implant surfaces under adjustable flow conditions. Frontiers in Microbiology. 17. doi: 10.3389/fmicb.2026.1751315. Full text in Research Archive Show summary

  Natural biofilms are typically composed of a mix of different microbial species and are often exposed to strong shear forces resulting from liquid flow. Simple biofilm models that attempt to study biofilms are based on a single species and on static growth conditions. To overcome these limitations, we developed a modular dual-loop reactor that decouples bacterial cultivation from hydrodynamic exposure, enabling independent control of nutrient availability (and thus, cell density) and flow rate (and thus, shear stress). Importantly, the system allows for testing different surface materials in a systematic manner. To validate our setup, we used a community of six keystone members of oral biofilms in conjunction with titanium materials of defined roughness that mimic dental implant surfaces. We found that biofilm mass, robustness, and species distribution not only differ significantly between static and dynamic growth conditions, but also vary strongly with different flow velocities. The biofilms formed under flow could be separated into two fractions, one that washed away very easily, and a more robust, basal layer. At low shear forces, overall biofilm mass was the highest, but at the expense of biofilm robustness. At medium shear forces, the robust fraction of the biofilm had the highest relative content of extracellular matrix. At the highest flow rates, the biofilm mass was low, but late colonizers (represented by the oral pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans ) had the lowest relative abundance. This is in accordance with the concept that high flow of saliva reduces the risk of oral disease. Future applications of our system will include the systematic testing of antimicrobial coatings or surface design effects under defined flow regimes, opening the path toward better medical implants.

• Reese, Jan-Ole; Lund, Ingrid M. Castro; Haugen, Håvard Jostein; Saragliadis, Athanasios; Lyngstadaas, Ståle Petter & Linke, Dirk (2026). A dual-loop chemostat to investigate multi-species biofilms on different materials under adjustable flow conditions. Frontiers in Microbiology. 17. Full text in Research Archive Show summary

  Natural biofilms are typically composed of a mix of different microbial species and are often exposed to strong shear forces resulting from liquid flow. Simple biofilm models that attempt to study biofilms are based on a single species and on static growth conditions. To overcome these limitations, we developed a modular dual-loop reactor that decouples bacterial cultivation from hydrodynamic exposure, enabling independent control of nutrient availability (and thus, cell density) and flow rate (and thus, shear stress). Importantly, the system allows for testing different surface materials in a systematic manner. To validate our setup, we used a community of six keystone members of oral biofilms in conjunction with titanium materials of defined roughness that mimic dental implant surfaces. We found that biofilm mass, robustness, and species distribution not only differ significantly between static and dynamic growth conditions, but also vary strongly with different flow velocities. The biofilms formed under flow could be separated into two fractions, one that washed away very easily, and a more robust, basal layer. At low shear forces, overall biofilm mass was the highest, but at the expense of biofilm robustness. At medium shear forces, the robust fraction of the biofilm had the highest relative content of extracellular matrix. At the highest flow rates, the biofilm mass was low, but late colonisers (represented by the oral pathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans) had the lowest relative abundance. This is in accordance with the concept that high flow of saliva reduces the risk of oral disease. Future applications of our system will include the systematic testing of antimicrobial coatings or surface design effects under defined flow regimes, opening the path towards better medical implants.

• Wang, Qiang; Haugen, Håvard Jostein; Linke, Dirk; Lyngstadaas, Ståle Petter & Ma, Qianli (2026). Residuals of Chemical Cleaning Agents Impair Peri-Implant Cell Viability: An in Vitro Study. ACS Biomaterials Science and Engineering. doi: 10.1021/acsbiomaterials.5c01777. Full text in Research Archive Show summary

  Background: Chemical debridement agents are commonly used during the cleaning of implants for peri-implantitis treatment; however, how these agents affect lesion healing remains unclear. In addition, the dose- and time-dependent effects of these residuals on implant biocompatibility remain poorly understood. Materials and methods: We evaluated the effects of active compounds in commercial products-3% hydrogen peroxide (H2O2), 0.43% sodium hypochlorite (NaClO), and 0.12% chlorhexidine with 0.05% cetylpyridinium chloride (CHX-CPC) at graded dilutions on murine osteoblastic cells (MC3T3-E1), human gingival fibroblasts (HGFs), and human bone marrow mesenchymal stromal cells (hBMSCs). Cells were cultured for 24 h, then exposed to the agents for 2, 12, or 24 h. Cytotoxicity and viability were assessed using lactate dehydrogenase (LDH) release and CCK-8 assays, while cell morphology was examined by scanning electron microscopy (SEM). Apoptotic gene expression (BCL2, MCL1, BAX) was analyzed after 2 h using quantitative PCR. Results: At high concentrations, H2O2 and NaClO significantly reduced LDH activity in supernatant, likely due to oxidant-induced enzyme inactivation. All three agents inhibited cell viability in a dose- and time-dependent manner, accompanied by cell shrinkage and deformation. Among the tested cell types, hBMSCs displayed greater resistance to H2O2, maintaining proliferative viability at 0.15% (1:20 dilution). Gene expression analysis revealed that concentrated H2O2 and CHX-CPC downregulated BCL2 and MCL1 expression in MC3T3-E1 cells, with broader suppression of these genes observed in HGFs across all agents. In hBMSCs, high concentrations of the agents did not significantly reduce BCL2 and MCL1 levels. Conclusion: Residual chemical debridement agents, when inadequately removed, compromise the viability of cells in peri-implant tissues in a dose- and time-dependent manner. hBMSCs exhibited greater resistance to apoptosis than MC3T3-E1 cells and HGFs. Thorough removal of residual chemical cleaning agents after peri-implant debridement is therefore crucial to preserve the biocompatibility of the implant and the healing

• Lauretis, Angela De; Wang, Qiang; Santacroce, Marco; Thiede, Bernd; Ma, Qianli & Lyngstadaas, Ståle Petter [Show all 9 contributors for this article] (2025). A Comparative Study of the Impact of Chemical Debridement Products on the Proteomic Profile of the Salivary Pellicle and Cell Adhesion on OsseoSpeed Titanium Dental Implant Surfaces. ACS Applied Materials & Interfaces. ISSN 1944-8244. 17(39), p. 54592–54592. doi: 10.1021/acsami.5c14570. Full text in Research Archive
• Nysæther, Ingvild; Haugen, Håvard Jostein; Khassawna, Thaqif El; Jamous, Reem; Afnan, Shoresh & Santacroce, Marco [Show all 10 contributors for this article] (2025). Clinical Performance of Ultra‐Porous TiO2 Scaffold as Bone Graft Substitute in Human Alveolar Ridge Preservation—A Feasibility Study. Clinical Oral Implants Research. ISSN 0905-7161. doi: 10.1111/clr.70074. Full text in Research Archive Show summary

  Objectives This study evaluates the safety and osteoconductive potential of a ceramic TiO2 scaffold in human alveolar bone, hypothesising that placement in human extraction sockets is safe, supports bone ingrowth and preserves ridge dimensions. Material and Methods Nine subjects requiring the extraction of ≥ 1 premolar or molar tooth were enrolled. Full-thickness mucoperiosteal flaps were elevated. Following tooth extraction, porous ceramic TiO2 scaffolds were adjusted chair-side, placed into the extraction socket and covered by a resorbable collagen membrane. After 6 months of healing, before dental implant placement, a biopsy was performed at the site where the scaffold had been placed. Histomorphometric and micro-CT analyses were made. CBCT images were made at baseline and at 6 months to assess alveolar ridge dimensional changes. Implants placed in regenerated bone were followed for 21 months. Results Scaffold customisation with chairside adjustment was straightforward. No serious adverse events were observed during the 6 months following scaffold implantation. One scaffold was removed due to an early exposure, while the remaining 9 scaffolds successfully integrated. Two sites presented with minor soft tissue dehiscences at 1–2 weeks, which healed spontaneously. Micro-CT and histology confirmed new bone formation. Soft tissue healing was favourable, with no adverse reactions. Dimensional analysis revealed minimal changes in alveolar ridge width and height, indicating effective preservation of volume. Conclusions This clinical study confirms that TiO2 scaffolds are a safe and effective option for promoting bone regrowth and preserving volume in human alveolar bone, thereby facilitating bone formation and maintaining ridge dimensions post-extraction.

• Øvrebø, Øystein; Lyngstadaas, Ståle Petter; Khassawna, Thaqif El; Jamous, Reem; Ma, Qianli & Muñoz, Fernando [Show all 13 contributors for this article] (2025). Multiomics Comparison of Proline‐Rich Peptide‐Enhanced Hyaluronic Acid Gels Versus Conventional Regenerative Materials: An Early Wound‐Healing Model. Journal of Periodontal Research. ISSN 0022-3484. doi: 10.1111/jre.70032. Full text in Research Archive Show summary

  Aims To compare the early wound‐healing responses to crosslinked hyaluronic acid enriched with two proline‐rich peptides (P2, P6) against unmodified hyaluronic acid and the enamel‐matrix derivative (EMD) in a porcine gingival‐detachment model. Methods In six pigs, defects around premolars were treated with HA, HA + P2, HA + P6 or EMD. After 6 days, the sites were harvested and evaluated using histology, immunohistochemistry, multiplex cytokine assay and untargeted proteomics of the gels, which were examined, informing an integrated multiomics approach analysis. Results Both peptide formulations improved the composite histological score compared to HA alone, and HA + P6 matched EMD in suppressing oedema, TNF‐α staining and CD80 + macrophages while increasing mannose‐receptor labelling. Proteomics revealed that P2 upregulated actin (Q6QAQ1) and histone H2A (F2Z5L5), consistent with active remodelling, whereas EMD reduced trypsin and trypsinogen, indicating a more stabilised wound milieu; HA + P6 showed an intermediate yet favourable profile. IL‐6 levels were lower in both peptide groups and EMD than in HA, and all gels proved noncytotoxic, with HA + P6 enhancing cell viability. Conclusion HA + P6 suppressed TNF‐α and trypsin signalling while boosting M2‐linked markers and proresolution proteins to the same extent as EMD, whereas plain HA did not. Thus, adding a short proline‐rich peptide confers EMD‐like early immunomodulation on a fully synthetic HA carrier. These observations, although limited to 6‐day soft tissue healing, warrant longer studies in true periodontal regeneration models.

• Lauretis, Angela de; Wang, Qiang; Santacroce, Marco; Thiede, Bernd; Ma, Qianli & Lyngstadaas, Ståle Petter [Show all 9 contributors for this article] (2025). A Comparative Study of the Impact of Chemical Debridement Products on the Proteomic Profile of the Salivary Pellicle and Cell Adhesion on OsseoSpeed Titanium Dental Implant Surfaces. ACS Applied Materials & Interfaces. ISSN 1944-8244. 17, p. 54579–54592. doi: 10.1021/acsami.5c14570. Full text in Research Archive Show summary

  Background and objectives: Dental implants are commonly used for tooth replacement, with excellent success rates over 10 years. However, exposure to oral cavity bacteria makes them susceptible to biofilm accumulation, which can lead to peri-implant diseases. The salivary pellicle, a protein-rich layer formed on implant surfaces, mediates bacterial adhesion and cell attachment. Effective decontamination is essential for managing bacterial infections, yet no consensus exists on the best chemical agent. Understanding how chemical agents affect the pellicle proteomic profile may guide the selection of optimal treatments. Methods: We investigate the impact of chemical decontamination agents on the salivary pellicle on OsseoSpeed-like titanium dental implant surfaces using a BCA assay and proteomics, and on cell adhesion using human gingival fibroblasts (HGF) and human bone marrow mesenchymal stem cells (hBMSC). We compare the effects of hydrogen peroxide (H2O2), Poloxamer 407 (P407), P407 + H2O2 and sodium hypochlorite + amino acids (NaOCl + AA) using the salivary pellicle and a clean titanium surface as controls. By quantifying and identifying proteins on titanium surfaces after decontamination, this study reveals how chemical agents affect the salivary pellicle. Results: All products reduced the total protein on the surfaces, with the P407 + H2O2 hydrogel demonstrating lower protein variety and superior effectiveness in preventing surface recontamination. Not all proteins were removed during decontamination procedures, and unique proteins were detected in each experimental condition, suggesting protein readsorption depends on surface chemistry. P407 + H2O2 shows the highest enrichment in integrin- and cadherin-binding proteins upon recontamination. P407 and P407 + H2O2 promoted HGFs and hBMSCs attachment. Conversely, NaOCl + AA and H2O2 showed lower HGFs and hBMSCs counts. Conclusion: The P407 + H2O2 hydrogel had the strongest decontamination effect and limited surface recontamination. Each chemical agent produced a distinct proteomic profile. P407 and P407 + H2O2 promoted initial cell adhesion.

• Lauretis, Angela de; Agger, Anne Eriksson; Pal, Antara; Pedersen, Jan Skov; Szostak, Szymon Mikolaj & Lund, Reidar [Show all 10 contributors for this article] (2025). Balancing sterilization and functional properties in Poloxamer 407 hydrogels: comparing heat and radiation techniques. Regenerative Biomaterials. 12. doi: 10.1093/rb/rbaf005. Full text in Research Archive Show summary

  Poloxamer 407, also known as Pluronic® F127, is gaining interest in the cosmetic, biomedical, and pharmaceutical fields for its biocompatibility, safety, and thermosensitive properties. Ensuring sterility is critical in clinical applications, and sterilization is often preferred over aseptic processing. However, sterilization can impact the hydrogel's functional properties. In this study, we investigate the effects of steam heat (121°C, 20 min), dry heat (160°C, 1 h), gamma irradiation (25 kGy), and electron beam (e-beam) irradiation (15 kGy and 25 kGy) on a 30%w/v Poloxamer 407 hydrogel formulation. Our analysis encompasses gelling properties, pH, Fourier-transform infrared (FTIR) spectroscopy, Gel Permeation Chromatography (GPC), Small-angle X-ray scattering (SAXS), rheology, swelling, degradation by-products, and lactate dehydrogenase (LDH) release of the sterilised hydrogels, comparing them to a non-sterile counterpart. We demonstrated that heat sterilisation alters the hydrogel’s gelling and structural properties due to water evaporation and oxidation under harsh temperature conditions, especially when applying the dry heat method. Gamma irradiation proved unsuitable, resulting in an acidic and cytotoxic hydrogel due to oxidative degradation. In contrast, e-beam irradiation preserves the hydrogel's elasticity, gelling, and structural properties while enhancing mechanical resilience and moderating swelling. Therefore, e-beam irradiation within the 15 – 25 kGy range appears to be the most suitable method for sterilizing a 30%w/v Poloxamer 407 hydrogel.

• Wang, Qiang; Haugen, Håvard Jostein; Linke, Dirk; Lyngstadaas, Ståle Petter; Sigurjonsson, Olafur & Ma, Qianli (2025). Impact of different chemical debridement agents on early cellular responses to Titanium dental implants: a transcriptome-based In Vitro Study on Peri-implant tissue regeneration. Colloids and Surfaces B: Biointerfaces. ISSN 0927-7765. 253. doi: 10.1016/j.colsurfb.2025.114727. Full text in Research Archive Show summary

  Background Poor peri-implant health leads to biofilm accumulation, peri-implantitis, and bone loss. Chemical debridement may help maintain peri-implant health, but its effects on peri-implant cells remain unclear. Methods Five cleaning agents—hydrogen peroxide (H2O2), Poloxamer, H2O2 +Poloxamer, Perisolv, and Paroex—were applied on titanium (Ti) surfaces. Mouse pre-osteoblasts (MC3T3-E1), human gingival fibroblasts (HGF), and human bone marrow stromal cells (hBMSC) were cultured on agent-treated Ti surfaces for up to 120 minutes to assess morphology, cytotoxicity, adhesion, and proliferation. RNA sequencing was performed on hBMSC. Results Except for Poloxamer, all treatments inhibited cellular spreading. Paroex increased cytotoxicity and inhibited proliferation. Perisolv impaired hBMSC adhesion and variably affected proliferation. H2O2, alone or with Poloxamer, elevated cytotoxicity and inhibited adhesion in hBMSCs but not MC3T3-E1 or HGF. In contrast, Poloxamer-treated Ti surfaces enhanced adhesion and proliferation across all cell types. RNA sequencing revealed that oxidant-based treatments (H2O2, H2O2 +Poloxamer, Perisolv) suppressed key genes for proliferation (HMGA2, JAG1, NOTCH1, YAP1, TBX3), anti-apoptosis (MCL1, BCL2L2), and adhesion (ITGA2, ITGB3, SPP1), while inhibiting MAPK, PI3K-Akt, and pluripotency pathways. Conclusion Commercial agents like Perisolv and Paroex impair hBMSC function, with Paroex demonstrating significant cytotoxicity. H2O2 exhibits toxicity, particularly to hBMSCs. Poloxamer improves cell attachment and growth. Given these findings, careful selection of debridement agents is critical to balance cleaning efficacy and cytocompatibility. The adverse effects on hBMSCs necessitate prompt removal postapplication. Further research on biomaterials supporting tissue regeneration postdebridement is needed to restore peri-implant health.

• Lauretis, Angela de; Santacroce, Marco; Ellingsen, Jan Eirik; Lyngstadaas, Ståle Petter; Linke, Dirk & Haugen, Håvard Jostein (2025). Surface-specific outcomes of mechanical debridement with titanium, chitosan and nitinol brushes on titanium dental implant surfaces. Journal of Dentistry. ISSN 0300-5712. doi: 10.1016/j.jdent.2025.106010. Full text in Research Archive Show summary

  Objectives Dental implants are susceptible to peri‑implant inflammation caused by bacterial biofilms, with surface properties playing a key role in bacterial adhesion and osseointegration. While mechanical debridement is essential for biofilm removal, consensus on the optimal tool remains limited. In this study, we evaluate the impact of a titanium, a chitosan and a nitinol brush on the surface properties of four titanium dental implant surfaces: OsseoSpeed®-like, SLActive®-like, machined, and polished. Methods Profilometry, contact angle measurements, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX) and X-ray photoelectron spectroscopy (XPS) were used to assess the surface properties and chemistry. Results SEM and profilometry revealed that the titanium and nitinol brushes altered the morphology and topography of the rough OsseoSpeed®-like and SLActive®-like surfaces, while these effects were less pronounced on machined surfaces. Conversely, the chitosan brush caused minimal changes, but its bristles wore down quickly by physical abrasion, increasing surface carbon as detected by EDX and identified by XPS as organic material. Conversely, XPS confirmed that carbon contamination in samples treated with metal brushes was primarily environmental. The increased hydrophobicity observed across all groups was linked to carbon contamination. Polished surfaces remained unaffected by mechanical debridement. Conclusions The chitosan brush showed minimal surface alterations, but the rapid bristle wear left organic residues that increased hydrophobicity. The titanium and nitinol brushes caused more pronounced surface changes, while contributing to increased hydrophobicity through environmental carbon contamination during debridement. Clinical significance Dental implant surface properties, including topography, morphology, wettability, and surface chemistry, play a critical role in bacterial adhesion and osseointegration. Selecting an optimal mechanical debridement instrument requires balancing the effective removal of biofilm with the impact on the implant surface properties.

• Tien, Nguyen D.; Geng, Tianxiang; Coelho, David José Caetano; Reseland, Janne Elin; Lyngstadaas, Ståle Petter & Blaker, Jonathan James [Show all 7 contributors for this article] (2025). Multilayer gradient chitosan fiber scaffolds for skin tissue regeneration with enhanced mechanical strength and cellular infiltration. Reactive & functional polymers. ISSN 1381-5148. 214. doi: 10.1016/j.reactfunctpolym.2025.106276. Full text in Research Archive Show summary

  Using the solution blow spinning technique, a trilayer structure scaffold was developed for skin tissue engineering. The scaffold, composed of chitosan/polyethylene oxide (CHI/PEO) fibers, mimicking the skin's natural structure, featuring a fiber diameter gradient ranging from 300 to 1200 nm and controlled porosity. Neutralization with potassium carbonate solution stabilized the chitosan-based fibers and enhanced their mechanical properties. The subsequent removal of PEO during neutralization created a porosity gradient (80–50%) across the scaffold layers, resulting in interconnected pores essential for cell infiltration and nutrient transport. The neutralized scaffolds enhanced mechanical performance with an ultimate tensile strength of 29.4 ± 4.8 MPa and Young’s modulus of 6.5 ± 1.1 MPa. The toughness was found to be 2.3 ± 1.0 MJ/m³. The gradient design closely mimics aspects of the skin's extracellular matrix. It substantially enhances the scaffold’s mechanical integrity—doubling tensile strength, Young’s modulus, and toughness compared to the as-spun structure—while preserving the essential flexibility required for dynamic wound environments. In vitro evaluations using co-cultures of normal human dermal fibroblasts (NHDF) and human epidermal keratinocytes (HEKa) demonstrated suitable cell viability, adhesion, and proliferation on the scaffold. Moreover, confocal imaging confirmed HEKa cellular infiltration throughout the more porous scaffold parts and dense NHDF layers on the less porous fiber layer, effectively mimicking the spatial organization of native skin layers. Our results underscore the significant potential of this gradient chitosan fiber scaffold as a scalable and versatile platform for skin tissue engineering. This innovative scaffold offers a promising new strategy for accelerating wound healing and achieving durable tissue regeneration by seamlessly integrating superior mechanical performance with enhanced cellular dynamics.

• Hussain, Badra; Simm, Roger; Bueno, Jaime; Giannettou, Savvas; Naemi, Ali-Oddin & Lyngstadaas, Ståle Petter [Show all 7 contributors for this article] (2024). Biofouling on titanium implants: a novel formulation of poloxamer and peroxide for in situ removal of pellicle and multi-species oral biofilm. Regenerative Biomaterials. 11. doi: 10.1093/rb/rbae014. Full text in Research Archive Show summary

  Eradicating biofouling from implant surfaces is essential in treating peri-implant infections, as it directly addresses the microbial source for infection and inflammation around dental implants. This controlled laboratory study examines the effectiveness of the four commercially available debridement solutions (EDTA (Prefgel®), NaOCl (Perisolv®), H2O2 (Sigma-Aldrich), and Chlorhexidine (GUM® Paroex®)) in removing the acquired pellicle, preventing pellicle re-formation, and removing of a multi-species oral biofilm growing on a titanium implant surface, and compare the results with the effect of a novel formulation of a peroxide activated Poloxamer gel (Nubone® Clean). Evaluation of pellicle removal and re-formation was conducted using Scanning Electron Microscope (SEM), Energy Dispersive X-ray Spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS) to assess the surface morphology, elemental composition, and chemical surface composition. Hydrophilicity was assessed through contact angle measurements. The multi-species biofilm model included Streptococcus oralis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans, reflecting the natural oral microbiome's complexity. Biofilm biomass was quantified using safranin staining, biofilm viability was evaluated using confocal laser scanning microscopy, and SEM was used for morphological analyses of the biofilm. Results indicated that while no single agent completely eradicated the biofilm, the Poloxamer gel activated with H2O2 exhibited promising results. It minimised re-contamination of the pellicle by significantly lowering the contact angle, indicating enhanced hydrophilicity. This combination also showed a notable reduction in carbon contaminants, suggesting the effective removal of organic residues from the titanium surface, in addition to effectively reducing viable bacterial counts. In conclusion, the Poloxamer gel + H2O2 combination emerged as a promising chemical decontamination strategy for peri-implant diseases. It underlines the importance of tailoring treatment methods to the unique microbial challenges in peri-implant diseases and the necessity of combining chemical decontaminating strategies with established mechanical cleaning procedures for optimal management of peri-implant diseases.

• Lauretis, Angela De; Øvrebø, Øystein; Romandini, Mario; Lyngstadaas, Ståle Petter; Rossi, Filippo & Haugen, Håvard Jostein (2024). From Basic Science to Clinical Practice: A Review of Current Periodontal/Mucogingival Regenerative Biomaterials. Advanced Science. doi: 10.1002/advs.202308848. Full text in Research Archive Show summary

  Periodontitis is a dysbiosis-driven inflammatory disease affecting the tooth-supporting tissues, characterized by their progressive resorption, which can ultimately lead to tooth loss. A step-wise therapeutic approach is employed for periodontitis. After an initial behavioural and non-surgical phase, intra-bony or furcation defects may be amenable to regenerative procedures. This review discusses the regenerative technologies employed for periodontal regeneration, highlighting the current limitations in the field and future research areas. Our search, performed on the MEDLINE database, has identified the available biomaterials, including biologicals (autologous platelet concentrates, hydrogels), bone grafts (pure or putty), and membranes. Biologicals and bone grafts have been critically analysed in terms of composition, mechanism of action, and clinical applications. Although a certain degree of periodontal regeneration is predictable in intra-bony and class II furcation defects, complete defect closure is hardly achieved. Moreover, treating class III furcation defects remains challenging. We discuss the key properties required for functional regeneration, and none of the commercially available biomaterials possess all the ideal characteristics. Therefore, research is needed to promote the advancement of more effective and targeted regenerative therapies for periodontitis. Lastly, we suggest improving the design and reporting of clinical studies by strictly adhering to the CONSORT 2010 statement.

• Gamage, Thilini Hansamali Gamage Yaddehi; Grabmayr, Herwig; Horvath, Ferdinand; Fahrner, Marc; Misceo, Doriana & Louch, William Edward [Show all 21 contributors for this article] (2023). A single amino acid deletion in the ER Ca2+ sensor STIM1 reverses the in vitro and in vivo effects of the Stormorken syndrome-causing R304W mutation. Science Signaling. ISSN 1945-0877. 16(771). doi: 10.1126/scisignal.add0509. Full text in Research Archive
• Hussain, Badra; Khan, Sadia Nazir; Agger, Anne Eriksson; Ellingsen, Jan Eirik; Lyngstadaas, Ståle Petter & Bueno, Jaime [Show all 7 contributors for this article] (2023). A Comparative Investigation of Chemical Decontamination Methods for In-Situ Cleaning of Dental Implant Surfaces. Journal of Functional Biomaterials. 14(8). doi: 10.3390/jfb14080394. Full text in Research Archive Show summary

  Surface chemistry evaluation is crucial in assessing the efficacy of chemical decontamination products for titanium implants. This study aimed to investigate the effectiveness of chemical decontamination solutions in cleaning a contaminated dental implant surface and to evaluate the potential of combining Pluronic gel with hydrogen peroxide (NuBone®Clean) by evaluating pellicle disruption and re-formation on implant surfaces. In addition, ensuring safety with in vitro and human testing protocols. X-ray Photoelectron Spectroscopy (XPS) was utilised for surface analysis. All the tested gels had some effect on the surface cleanness except for PrefGel®. Among the tested chemical decontamination candidates, NuBone®Clean demonstrated effectiveness in providing a cleaner titanium surface. Furthermore, none of the tested chemical agents exhibited cytotoxic effects, and the safety assessment showed no adverse events. The results of this study highlight the significance of conducting comprehensive evaluations, encompassing safety and efficacy, before introducing new chemical agents for dental treatments. The findings suggest that NuBone®Clean shows potential as a chemical decontamination solution for implant surfaces. However, further investigation through randomised clinical trials is necessary. By adhering to rigorous testing protocols, the development of safe and efficient chemical decontamination strategies can be advanced, benefiting patients and promoting progress in implant dentistry

• Spoutil, Frantisek; Aranaz-Novaliches, Goretti; Prochazkova, Michaela; Wald, Tomas; Novosadova, Vendula & Kasparek, Petr [Show all 14 contributors for this article] (2023). Early evolution of enamel matrix proteins is reflected by pleiotropy of physiological functions. Scientific Reports. 13(1). doi: 10.1038/s41598-023-28388-4. Full text in Research Archive Show summary

  Highly specialized enamel matrix proteins (EMPs) are predominantly expressed in odontogenic tissues and diverged from common ancestral gene. They are crucial for the maturation of enamel and its extreme complexity in multiple independent lineages. However, divergence of EMPs occured already before the true enamel evolved and their conservancy in toothless species suggests that non-canonical functions are still under natural selection. To elucidate this hypothesis, we carried out an unbiased, comprehensive phenotyping and employed data from the International Mouse Phenotyping Consortium to show functional pleiotropy of amelogenin, ameloblastin, amelotin, and enamelin, genes, i.e. in sensory function, skeletal morphology, cardiovascular function, metabolism, immune system screen, behavior, reproduction, and respiratory function. Mice in all KO mutant lines, i.e. amelogenin KO, ameloblastin KO, amelotin KO, and enamelin KO, as well as mice from the lineage with monomeric form of ameloblastin were affected in multiple physiological systems. Evolutionary conserved motifs and functional pleiotropy support the hypothesis of role of EMPs as general physiological regulators. These findings illustrate how their non-canonical function can still effect the fitness of modern species by an example of influence of amelogenin and ameloblastin on the bone physiology.

• Antich-Rosselló, Miquel; Forteza-Genestra, Maria Antònia; Rønold, Hans Jacob; Lyngstadaas, Ståle Petter; García-González, Mario & Permuy, María [Show all 10 contributors for this article] (2023). Platelet-derived extracellular vesicles formulated with hyaluronic acid gels for application at the bone-implant interface: An animal study. Journal of orthopaedic translation. ISSN 2214-0328. 40, p. 72–79. doi: 10.1016/j.jot.2023.05.009. Full text in Research Archive
• Tien, Nguyen D.; Geng, Tianxiang; Heyward, Catherine Anne; Reseland, Janne Elin; Lyngstadaas, Ståle Petter & Blaker, Jonathan James [Show all 7 contributors for this article] (2022). Solution blow spinning of highly deacetylated chitosan nanofiber scaffolds for dermal wound healing. Materials Science and Engineering C: Materials for Biological Applications. ISSN 0928-4931. 137. doi: 10.1016/j.bioadv.2022.212871. Full text in Research Archive Show summary

  Biocompatible fibrous scaffolds based on highly deacetylated chitosan were fabricated using high-throughput solution blow spinning. Scanning electron microscopy analysis revealed that the chitosan nanofiber scaffolds had ultrafine and continuous fibers (300–1200 nm) with highly interconnected porous structures (30–75% porosity), mimicking some aspects of the native extracellular matrix in skin tissue. Post-treatment of as-spun nanofibers with aqueous potassium carbonate solution resulted in a fibrous scaffold with a high chitosan content that retained its fibrous structural integrity for cell culture. Analysis of the mechanical properties of the chitosan nanofiber scaffolds in both dry and wet conditions showed that their strength and durability were sufficient for wound dressing applications. Significantly, the wet scaffold underwent remarkable elastic deformation during stretch such that the elongation at break dramatically increased to up to 44% of its original length, showing wavy fiber morphology near the break site. The culture of normal human dermal fibroblast cells onto scaffolds for 1–14 days demonstrated that the scaffolds were highly compatible and a suitable platform for cell adhesion, viability, and proliferation. Secretion profiles of wound healing-related proteins to the cell culture medium demonstrated that chitosan fibers were a promising scaffold for wound healing applications. Overall, the dense fibrous network with high porosity of the chitosan nanofiber scaffold and their mechanical properties indicate that they could be used to design and fabricate new materials that mimic the epidermis layer of natural skin.

• Mortier, Claudio; Costa, Dora C.S.; Oliveira, Mariana B; Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter & Blaker, Jonny j [Show all 7 contributors for this article] (2022). Advanced hydrogels based on natural macromolecules: chemical routes to achieve mechanical versatility. Materials Today Chemistry. ISSN 2468-5194. 26. doi: 10.1016/j.mtchem.2022.101222. Full text in Research Archive Show summary

  Advances in synthetic routes to chemically modify natural macromolecules such as polysaccharides and proteins have allowed designing functional hydrogels able to tackle current challenges in the biomedical field. Hydrogels are hydrophilic three-dimensional systems able to absorb or retain a large volume of water, prepared from a low percentage of precursor macromolecules. The typical fragile elastic structure of common hydrogel formulations often limits their usage. Three main fabrication strategies involving several compounds or multi-modified materials known as double networks (DNs), dual-crosslinked networks (DC) and interpenetrating networks (IPN) have been explored to impart mechanical strength to hydrogels. Widely investigated for synthetic polymers, these approaches allow obtaining added-value hydrogels with a large spectrum of mechanical properties. Advances in the development of such hydrogels with biomacromolecules as main constituent materials have enabled the fabrication of hydrogels with improved key properties for medical use, including biocompatibility, controlled release of active substances and tailored biodegradability, while exploring sustainable sources. This review describes recent advances in the use of proteins, as well as natural and semi-synthetic polymers for the fabrication of hydrogels for biomedical applications. Structures processed via DN, DC or IPN strategies are reviewed, and emphasis is given to the type of chemical modifications and reactions, as well as the covalent and non-covalent interactions/bonds involved in those mechanisms.

• Zouharova, Monika; Vymetal, Jiri; Bednarova, Lucie; Vanek, Ondrej; Herman, Petr & Vetyskova, Veronika [Show all 10 contributors for this article] (2021). Intrinsically disordered protein domain of human ameloblastin in synthetic fusion with calmodulin increases calmodulin stability and modulates its function. International Journal of Biological Macromolecules. ISSN 0141-8130. 168, p. 1–12. doi: 10.1016/j.ijbiomac.2020.11.216. Full text in Research Archive
• Rahmati, Maryam; Stoetzel, Sabine; Khassawna, Thaqif El; 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. 52, p. 63–79. doi: 10.1016/j.mattod.2021.12.001. Full text in Research Archive 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.

• 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. Full text in Research Archive Show summary

  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 [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 (Beijing). ISSN 2095-8099. 13, p. 197–208. doi: 10.1016/j.eng.2021.01.010. Full text in Research Archive Show summary

  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.

• Hussain, Badra; Haugen, Håvard Jostein; Aass, Anne Merete; Alonso, Mariano Sanz; 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. 2(726607). doi: 10.3389/fdmed.2021.726607. Full text in Research Archive Show summary

  Objectives: Peri-implant tissue maintenance and treatment is becoming a serious challenge in implantology. With increasing numbers of implants being placed, more cases of peri-implant mucositis and peri-implantitis is seen. A digital survey on peri-implant disease management was issued to experts in periodontology and implantology to identify the tools and procedures most commonly used today to treat peri-implant diseases and successfully manage peri-implant health. The primary aim was to assess whether there is consensus in the choice of treatment to manage peri-implant diseases and to prevent their recurrence once treated. The secondary aim was to obtain insight into future protocols and /or devices, and the research and development needed. Materials and Methods: Participants in this digital survey were professionals specialising in periodontology, oral surgery, and implant dentistry. The questionnaire included both a series of closed- and open-ended questions. A total of 16 countries participated. The survey was sent by e-mail to 70 individuals, 66 received the survey and 37 of receivers responded, two of the participants were excluded due to insufficient filling of the survey. In the end 35 respondents completed the survey. Results: Respondents agree that the efficacy of mechanical and chemical decontamination of implant surfaces needs to be improved and better documented. It is a common opinion that the current remedies, mostly adapted from periodontal practises, do not provide effective and reliable clinical outcomes when treating peri-implant ailments. There is a general agreement amongst experts that regularly scheduled (3–6-month intervals) maintenance treatments are essential for maintaining peri-implant health in patients experiencing implant complications. Respondents are also concerned about unnecessary use of systemic antibiotics for managing peri-implant health. Conclusion: Regardless of agreements in parts, there was no observed consensus on the most effective treatment options for treating peri-implantitis. The experts all agree it is an urgent need for well-designed, long-term follow-up randomised and controlled clinical trials comparing interventions to provide an evidence-based strategy for peri-implant health management.

• 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 1226-4601. 25(43). doi: 10.1186/s40824-021-00245-3. Full text in Research Archive Show summary

  Background Insufficient bone volume around an implant is a common obstacle when dental implant treatment is considered. Limited vertical or horizontal bone dimensions may lead to exposed implant threads following placement or a gap between the bone and implant. This is often addressed by bone augmentation procedures prior to or at the time of implant placement. This study evaluated bone healing when a synthetic TiO2 block scaffold was placed in circumferential peri-implant defects with buccal fenestrations. Methods The mandibular premolars were extracted and the alveolar bone left to heal for 4 weeks prior to implant placement in six minipigs. Two cylindrical defects were created in each hemi-mandible and were subsequent to implant placement allocated to treatment with either TiO2 scaffold or sham in a split mouth design. After 12 weeks of healing time, the samples were harvested. Microcomputed tomography (MicroCT) was used to investigate defect fill and integrity of the block scaffold. Distances from implant to bone in vertical and horizontal directions, percentage of bone to implant contact and defect fill were analysed by histology. Results MicroCT analysis demonstrated no differences between the groups for defect fill. Three of twelve scaffolds were partly fractured. At the buccal sites, histomorphometric analysis demonstrated higher bone fraction, higher percentage bone to implant contact and shorter distance from implant top to bone 0.5 mm lateral to implant surface in sham group as compared to the TiO2 group. Conclusions This study demonstrated less bone formation with the use of TiO2 scaffold block in combination with implant placement in cylindrical defects with buccal bone fenestrations, as compared to sham sites.

• Tien, Nguyen D.; 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 1431-5157. 26(2683), p. 1–24. doi: 10.3390/molecules26092683. Full text in Research Archive Show summary

  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.

• Rahmati, Maryam; Frank, Matthias Johannes; Walter, Martin Sebastian; Cabrer, Marta Monjo; 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). 3, p. 5169–5181. doi: 10.1021/acsabm.0c00608. Full text in Research Archive Show summary

  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; 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.

• 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. doi: 10.3389/fcell.2020.619111. Full text in Research Archive Show summary

  Bone defect is a noteworthy health problem and is the second most transplanted tissue after blood. Numerous bone grafts are designed and applied in clinics. Limitations, however, from different aspects still exist, including limited supply, mechanical strength, and bioactivity. In this study, two biomimetic peptides (P2 and P6) are incorporated into a composite bioactive xeno hybrid bone graft named SmartBonePep ® , with the aim to increase the bioactivity of the bone graft. The results, which include cytotoxicity, proliferation rate, confocal microscopy, gene expression, and protein qualification, successfully prove that the SmartBonePep ® has multi-modal biological effects on human mesenchymal stem cells from bone marrow. The effective physical entrapment of P6 into a composite xeno-hybrid bone graft, withstanding manufacturing processes including exposure to strong organic solvents and ethylene oxide sterilization, increases the osteogenic potential of the stem cells as well as cell attachment and proliferation. P2 and P6 both show a strong biological potential and may be future candidates for enhancing the clinical performance of bone grafts.

• 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.

• 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. 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.

• 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), p. 92–102. doi: 10.1111/jcpe.13058. Full text in Research Archive Show summary

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

• Gamage, Thilini Hansamali Gamage Yaddehi; Lengle, Emma; Gunnes, Gjermund; Pullisaar, Helen; Holmgren, Asbjørn & Reseland, Janne Elin [Show all 16 contributors for this article] (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. Full text in Research Archive
• Giannobile, William V; Berglundh, Tord; Al-Nawas, Bilal; Araujo, Mauricio; Bartold, P Mark & Bouchard, Philippe [Show all 18 contributors for this article] (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), p. 6–11. doi: 10.1111/jcpe.13130. Full text in Research Archive
• Stakkestad, Øystein; Heyward, Catherine Anne; Lyngstadaas, Ståle Petter; Medin, Tirill; Vondrasek, Jiri & Lian, Aina-Mari [Show all 8 contributors for this article] (2018). An ameloblastin C-terminus variant is present in human adipose tissue. Heliyon. 4(12). doi: 10.1016/j.heliyon.2018.e01075. Full text in Research Archive Show summary

  Objective: Transcriptional regulatory elements in the ameloblastin (AMBN) promoter indicate that adipogenesis may influence its expression. The objective here was to investigate if AMBN is expressed in adipose tissue, and have a role during differentiation of adipocytes. Design: AMBN expression was examined in adipose tissue and adipocytes by real-time PCR and ELISA. Distribution of ameloblastin was investigated by immunofluorescence in sections of human subcutaneous adipose tissue. The effect of recombinant proteins resembling AMBN and its processed products on proliferation of primary human pre-adipocytes and murine 3T3-L1 cell lines was measured by [3H]-thymidine incorporation. The effect on adipocyte differentiation was evaluated by the expression profile of the adipogenic markers PPARγ and leptin, and the content of lipids droplets (Oil-Red-O staining). Results: AMBN was found to be expressed in human adipose tissue, human primary adipocytes, and in 3T3-L1 cells. The C-terminus of the AMBN protein and a 45 bp shorter splice variant was identified in human subcutaneous adipose tissue. The expression of AMBN was found to increase four-fold during differentiation of 3T3-L1 cells. Administration of recombinant AMBN reduced the proliferation, and enhanced the expression of PPARγ and leptin in 3T3-L1 and human pre-adipocytes, respectively. Conclusions: The AMBN C-terminus variant was identified in adipocytes. This variant may be encoded from a short splice variant. Increased expression of AMBN during adipogenesis and its effect on adipogenic factors suggests that AMBN also has a role in adipocyte development.

• Córdoba, Alba; Manzanaro-Moreno, Nahuel; Colom, Carme; Rønold, Hans Jacob; Lyngstadaas, Ståle Petter & Monjo, Marta [Show all 7 contributors for this article] (2018). Quercitrin Nanocoated Implant Surfaces Reduce Osteoclast Activity In Vitro and In Vivo. International Journal of Molecular Sciences. ISSN 1661-6596. 19(11). doi: 10.3390/ijms19113319. Full text in Research Archive Show summary

  In this study, the effect on osteoclast activity in vitro and in vivo of titanium implants that were coated with quercitrin was evaluated. Titanium surfaces were covalently coated with the flavonoid quercitrin. The effect of the surfaces on osteoclastogenesis was first tested in vitro on RAW264.7 cells that were supplemented with receptor activator of nuclear factor kappa-B ligand (RANKL) to generate osteoclast-like cells by tartrate-resistant acid phosphatase (TRAP) inmunostaining after five days of culture, and by analysis of the mRNA expression levels of markers related to bone resorption after seven days of culture. A rabbit tibial model was used to evaluate the in vivo biological response to the implant surfaces after eight weeks of healing, analyzing the lactate dehydrogenase (LDH) and the alkaline phosphatase (ALP) activities in the wound fluid that were present at the implant interface and the peri-implant bone mRNA expression levels of several markers related to inflammation, bone resorption and osteoblast-osteoclast interaction. No differences between groups and control surfaces were found in the wound fluid analyses. Moreover, quercitrin implant surfaces significantly decreased the expression of osteoclast related genes in vitro (Trap, CalcR, Ctsk, H+ATPase, Mmp9) and in vivo (Ctsk, H+ATPase, Mmp9) as well as the expression of RankL in vivo. Moreover, quercitrin surfaces were not cytotoxic for the cells. Thus, quercitrin implant surfaces were biocompatible and decreased osteoclastogenesis in vitro and in vivo. This could be used to improve the performance of dental implants.

• 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), p. 1086–1094. doi: 10.1016/j.ijom.2018.02.007. Full text in Research Archive Show summary

  The use of two particulate bone graft substitute materials in experimental narrow marginal peri-implant bone defects was investigated with respect to early bone healing and implant stability. Porous titanium granules, oxidized white porous titanium granules (WPTG), and demineralized bovine bone mineral (DBBM) were characterized in vitro, after which the two latter materials were tested in experimental peri-implant bone defects in six minipigs, with empty defects as control. After mandibular premolar extraction, the top 5 mm of the alveoli were widened to 6 mm in diameter, followed by the placement of six implants, three on each side, in each pig. Six weeks of healing was allowed. The WPTG showed better mechanical properties. No significant differences in resonance frequency analysis were found directly after compacting or healing, and similar quantities of defect bone formation were observed on micro-computed tomography for all groups. Histomorphometric analysis demonstrated a more coronal bone-to-implant contact in the DBBM group, which also displayed more defect bone fill as compared to the WPTG group. The better mechanical properties observed for WPTG appear of negligible relevance for the early stability and osseointegration of implants.

• Johnsen, Gaute Floer; Thieu, Minh Khai Le; Hussain, Badra; Pamula, Elzbieta; Reseland, Janne Elin & Lyngstadaas, Ståle Petter [Show all 7 contributors for this article] (2017). Own brand label restorative materials - A false bargain? Journal of Dentistry. ISSN 0300-5712. 56, p. 84–98. doi: 10.1016/j.jdent.2016.11.004. Full text in Research Archive Show summary

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

• 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), p. 424–431. doi: 10.1111/clr.12815. Full text in Research Archive
• 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. 8. doi: 10.3389/fphys.2017.00058. Full text in Research Archive Show summary

  During amelogenesis the extracellular enamel matrix protein AMBN is quickly processed into 17 kDa (N-terminus) and 23 kDa (C-terminus) fragments. In particular, alternatively spliced regions derived by exon 5/6 within the N-terminus region are known to be critical in biomineralization. Human mesenchymal stem cells (hMSC) also express and secrete AMBN, but it is unclear if this expression has effects on the hMSC themselves. If, as suggested from previous findings, AMBN act as a signaling molecule, such effects could influence hMSC growth and differentiation, as well as promoting the secretion of other signaling proteins like cytokines and chemokines. If AMBN is found to modulate stem cell behavior and fate, it will impact our understanding on how extracellular matrix molecules can have multiple roles during development ontogenesis, mineralization and healing of mesenchymal tissues. Here we show that synthetic peptides representing exon 5 promote hMSC proliferation. Interestingly, this effect is inhibited by the application of a 15 aa peptide representing the alternatively spliced start of exon 6. Both peptides also influence gene expression of RUNX2 and osteocalcin, and promote calcium deposition in cultures, indicating a positive influence on the osteogenic capacity of hMSC. We also show that the full-length AMBN-WT and N-terminus region enhance the secretion of RANTES, IP-10, and IL-8. In contrast, the AMBN C-terminus fragment and the exon 5 deleted AMBN (DelEx5) have no detectable effects on any of the parameters investigated. These findings suggest the signaling effect of AMBN is conveyed by processed products, whereas the effect on proliferation is differentially modulated through alternative splicing during gene expression.

• 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. 8. doi: 10.3389/fphys.2017.00531. Full text in Research Archive Show summary

  Ameloblastin (AMBN), an important component of the self-assembled enamel extra cellular matrix, contains several in silico predicted phosphorylation sites. However, to what extent these sites actually are phosphorylated and the possible effects of such post-translational modifications are still largely unknown. Here we report on in vitro experiments aimed at investigating what sites in AMBN are phosphorylated by casein kinase 2 (CK2) and protein kinase A (PKA) and the impact such phosphorylation has on self-assembly and calcium binding. All predicted sites in AMBN can be phosphorylated by CK2 and/or PKA. The experiments show that phosphorylation, especially in the exon 5 derived part of the molecule, is inversely correlated with AMBN self-assembly. These results support earlier findings suggesting that AMBN self-assembly is mostly dependent on the exon 5 encoded region of the AMBN gene. Phosphorylation was significantly more efficient when the AMBN molecules were in solution and not present as supramolecular assemblies, suggesting that post-translational modification of AMBN must take place before the enamel matrix molecules self-assemble inside the ameloblast cell. Moreover, phosphorylation of exon 5, and the consequent reduction in self-assembly, seem to reduce the calcium binding capacity of AMBN suggesting that post-translational modification of AMBN also can be involved in control of free Ca2+ during enamel extra cellular matrix biomineralization. Finally, it is speculated that phosphorylation can provide a functional crossroad for AMBN either to be phosphorylated and act as monomeric signal molecule during early odontogenesis and bone formation, or escape phosphorylation to be subsequently secreted as supramolecular assemblies that partake in enamel matrix structure and mineralization.

• Verket, Anders; Müller, Benjamin; Wohlfahrt, Johan Caspar; Lyngstadaas, Ståle Petter; Ellingsen, Jan Eirik & Haugen, Håvard Jostein [Show all 7 contributors for this article] (2016). TiO2 scaffolds in peri-implant dehiscence defects: an experimental pilot study. Clinical Oral Implants Research. ISSN 0905-7161. 27(10), p. 1200–1206. doi: 10.1111/clr.12725. Full text in Research Archive
• Villa, Oscar; Wohlfahrt, Johan Caspar; Koldsland, Odd Carsten; Brookes, Steven J; Lyngstadaas, Ståle Petter & Aass, Anne Merete [Show all 7 contributors for this article] (2016). EMD in periodontal regenerative surgery modulates cytokine profiles: A randomised controlled clinical trial. Scientific Reports. 6, p. 1–9. doi: 10.1038/srep23060. Full text in Research Archive Show summary

  The enamel matrix derivative (EMD) contains hundreds of peptides in different levels of proteolytic processing that may provide a range of biological effects of importance in wound healing. The aim of the present study was to compare the effect of EMD and its fractions on the cytokine profiles from human gingival fibroblasts in vitro and in gingival crevicular fluid (GCF) in a randomized controlled split-mouth clinical study (n = 12). Levels of cytokines in cell culture medium and in GCF were measured by Luminex over a 2-week period. In the clinical study, levels of pro-inflammatory cytokines and chemokines were increased, whereas the levels of transforming growth factor-α (TGF-α) and platelet-derived growth factor-BB (PDGF-BB) were reduced. The in vitro study showed that EMD and its high and low molecular weight fractions reduced the secretion of pro-inflammatory cytokines and chemokines compared to untreated cells. EMD had an effect on levels of cytokines related to fibroplasia, angiogenesis, inflammation and chemotaxis both in vitro and in vivo, however, the anti-inflammatory effect induced by EMD observed in the in vitro study could not be confirmed clinically.

• Miron, Richard J.; Sculean, Anton; Cochran, David L.; Froum, Stuart; Zucchelli, Giovanni & Nemcovsky, Carlos [Show all 20 contributors for this article] (2016). Twenty years of enamel matrix derivative: the past, the present and the future. Journal of Clinical Periodontology. ISSN 0303-6979. 43(8), p. 668–683. doi: 10.1111/jcpe.12546. Full text in Research Archive
• Villa, Oscar; Wohlfahrt, Johan Caspar; Mdala, Ibrahimu; Petzold, Christiane; Reseland, Janne Elin & Snead, Malcolm L. [Show all 7 contributors for this article] (2015). Proline-rich peptide mimic effects of EMD in rat oral mucosal incisional wound healing. Journal of Periodontology. ISSN 0022-3492. 86(12), p. 1386–1395. doi: 10.1902/jop.2015.150207. Full text in Research Archive
• Xing, Rui; Witsø, Ingun Lund; Jugowiec, David; Tiainen, Hanna; Shabestari, Maziar & Lyngstadaas, Ståle Petter [Show all 8 contributors for this article] (2015). Antibacterial effect of doxycycline-coated dental abutment surfaces. Biomedical Materials. ISSN 1748-6041. 10(5), p. 55003–55012. doi: 10.1088/1748-6041/10/5/055003. Full text in Research Archive Show summary

  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.

• Villa, Oscar; Lyngstadaas, Ståle Petter; Monjo, Marta; Satué, María; Rønold, Hans Jacob & Petzold, Christiane [Show all 7 contributors for this article] (2015). Suture materials affect peri-implant bone healing and implant osseointegration. Journal of Oral Science. ISSN 1343-4934. 57(3), p. 219–227. doi: 10.2334/josnusd.57.219. Full text in Research Archive
• 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. 6, p. 1–11. doi: 10.1177/2041731415575857. Full text in Research Archive Show summary

  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.

• Córdoba, Alba; Satué, María; Gomez-Florit, Manuel; Hierro-Oliva, Margarita; Petzold, Christiane & Lyngstadaas, Ståle Petter [Show all 9 contributors for this article] (2015). Flavonoid-modified surfaces: Multifunctional bioactive biomaterials with osteopromotive, anti-inflammatory, and anti-fibrotic potential. Advanced Healthcare Materials. ISSN 2192-2640. 4(4), p. 540–549. doi: 10.1002/adhm.201400587. Full text in Research Archive
• 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), p. 649–656. doi: 10.1111/clr.12354. Full text in Research Archive Show summary

  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

• 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), p. 335–340. doi: 10.1111/eos.12201. Full text in Research Archive Show summary

  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.

• Lyngstadaas, Ståle Petter; Verket, Anders; Pinholt, Else Marie; Mertens, Christian; Haanæs, Hans R & Wall, Gert [Show all 8 contributors for this article] (2015). Titanium granules for augmentation of the maxillary sinus- a multicenter study. Clinical Implant Dentistry and Related Research. ISSN 1523-0899. 17, p. e594–e600. doi: 10.1111/cid.12291. Full text in Research Archive
• Gomez-Florit, Manuel; Xing, Rui; Ramis, Joana Maria; Taxt-Lamolle, Sebastien Francis Michel; Haugen, Håvard Jostein & Lyngstadaas, Ståle Petter [Show all 7 contributors for this article] (2014). Human gingival fibroblasts function is stimulated on machined hydrided titanium zirconium dental implants. Journal of Dentistry. ISSN 0300-5712. 42(1), p. 30–38. doi: 10.1016/j.jdent.2013.11.003. Full text in Research Archive Show summary

  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.

• Frank, Matthias Johannes; Walter, Martin Sebastian; Rubert, Marina; Thiede, Bernd; Cabrer, Marta Monjo & Reseland, Janne Elin [Show all 8 contributors for this article] (2014). Cathodic polarization coats titanium based implant materials with enamel matrix derivate (EMD). Materials. 7(3), p. 2210–2228. doi: 10.3390/ma7032210. Full text in Research Archive Show summary

  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.

• 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), p. 1389–1398. doi: 10.1002/jbm.a.34819. Full text in Research Archive Show summary

  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.

• Reikerås, Olav; Borgen, Pål; Reseland, Janne Elin & Lyngstadaas, Ståle Petter (2014). Changes in serum cytokines in response to musculoskeletal surgical trauma. BMC Research Notes. 7(1). doi: 10.1186/1756-0500-7-128. Full text in Research Archive
• Gordeladze, Jan Oxholm; Stakkestad, Øystein; Haugen, Sigrid; Reseland, Janne Elin; Syversen, Unni & Johnsen, Gaute Floer [Show all 10 contributors for this article] (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 Eberli, Daniel (Eds.), Cells and Biomaterials in Regenerative Medicine. IntechOpen. ISSN 9789535117315. doi: 10.5772/59149. Full text in Research Archive
• Walter, Martin Sebastian; Frank, Matthias Johannes; Satué, María; Cabrer, Marta Monjo; Rønold, Hans Jacob & Lyngstadaas, Ståle Petter [Show all 7 contributors for this article] (2014). Bioactive Implant Surface with Electrochemically Bound Doxycycline Promotes Bone Formation Markers In Vitro and In Vivo. Dental Materials. ISSN 0109-5641. 30(2), p. 200–214. doi: 10.1016/j.dental.2013.11.006. Full text in Research Archive Show summary

  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.

• 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), p. E100–E108. doi: 10.1111/clr.12070. Full text in Research Archive
• 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), p. 424–431. doi: 10.1111/jcpe.12229. Full text in Research Archive
• 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), p. 897–908. doi: 10.1177/0885328213486364. Full text in Research Archive Show summary

  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.

• Gomez-Florit, Manuel; Ramis, Joana Maria; Xing, Rui; Taxt-Lamolle, Sebastien Francis Michel; Haugen, Håvard Jostein & Lyngstadaas, Ståle Petter [Show all 7 contributors for this article] (2014). Differential response of human gingival fibroblasts to titanium- and titanium-zirconium-modified surfaces. Journal of Periodontal Research. ISSN 0022-3484. 49(4), p. 425–436. doi: 10.1111/jre.12121. Full text in Research Archive Show summary

  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.

• 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), p. 707–713. doi: 10.1111/clr.12130. Full text in Research Archive Show summary

  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.

• 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 1661-6596. 15(5), p. 7731–7749. doi: 10.3390/ijms15057731. Full text in Research Archive Show summary

  Enamel matrix derivative (EMD) has been found to induce reactive dentin formation; however the molecular mechanisms involved are unclear. The effect of EMD (5–50 µg/mL) on primary human pulp cells were compared to untreated cells and cells incubated with 10-8 M dexamethasone (DEX) for 1, 2, 3, 7, and 14 days in culture. Expression analysis using Affymetrix microchips demonstrated that 10 µg/mL EMD regulated several hundred genes and stimulated the gene expression of proteins involved in mesenchymal proliferation and differentiation. Both EMD and DEX enhanced the expression of amelogenin (amel), and the dentinogenic markers dentin sialophosphoprotein (DSSP) and dentin matrix acidic phosphoprotein 1 (DMP1), as well as the osteogenic markers osteocalcin (OC, BGLAP) and collagen type 1 (COL1A1). Whereas, only EMD had effect on alkaline phosphatase (ALP) mRNA expression, the stimulatory effect were verified by enhanced secretion of OC and COL1A from EMD treated cells, and increased ALP activity in cell culture medium after EMD treatment. Increased levels of interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant proteins (MCP-1) in the cell culture medium were also found. Consequently, the suggested effect of EMD is to promote differentiation of pulp cells and increases the potential for pulpal mineralization to favor reactive dentine formation.

• 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), p. 1647–1658. doi: 10.3233/BME-140978. Full text in Research Archive
• Verket, Anders; Lyngstadaas, Ståle Petter; Rasmusson, Lars; Haanæs, Hans R; Wallstrøm, M. & Wall, Gert [Show all 7 contributors for this article] (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), p. 721–728. doi: 10.11607/jomi.2853. Full text in Research Archive Show summary

  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.

• 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, p. 7–16. doi: 10.1016/j.apsusc.2013.04.059. Full text in Research Archive Show summary

  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 [Show all 7 contributors for this article] (2013). Coating of metal implant materials with strontium. Journal of Materials Science: Materials in Medicine. ISSN 0957-4530. 24(11), p. 2537–2548. doi: 10.1007/s10856-013-5007-1. Full text in Research Archive
• Lacruz, Rodrigo S; Brookes, Steven J; Wen, Xin; Jimenez, Jaime M; Vikman, Susanna & Hu, Ping [Show all 11 contributors for this article] (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), p. 672–687. doi: 10.1002/jbmr.1779. Full text in Research Archive

View all works in NVA

• Lund, Ingrid Maria Castro; Reese, Jan-Ole; Saragliadis, Athanasios; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein & Linke, Dirk (2025). Discovering the species-specific dynamics within a model biofilm system for peri-implantitis. Full text in Research Archive
• Reese, Jan-Ole; Lund, Ingrid Maria Castro; Haugen, Håvard Jostein; Saragliadis, Athanasios; Lyngstadaas, Ståle Petter & Linke, Dirk (2025). Development of a flow-controlled biofilm model to facilitate the testing of debridement treatments of dental implant surfaces. Full text in Research Archive
• Lauretis, Angela de; Santacroce, Marco; Hussain, Badra; Ma, Qianli; Ellingsen, Jan Eirik & Lyngstadaas, Ståle Petter [Show all 8 contributors for this article] (2025). A poloxamer-peroxide forumulation effectively removes pellicle and limits recontamination. Full text in Research Archive
• Lauretis, Angela de; Hussain, Badra; Ma, Qianli; Ellingsen, Jan Eirik; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2024). A comparative evaluation of chemical decontamination products on the cleanliness of dental implant surfaces using a dental pellicle model. Full text in Research Archive Show summary

  Dental implants are widely employed for tooth replacement, but complications such as peri-implant infections may arise due to bacterial adhesion and biofilm formation, facilitated by the protein-rich salivary pellicle formed on the implant surface. Ensuring the cleanliness of the implant surface is crucial for long-term success and maintenance of peri-implant health.

• Lauretis, Angela de; Lyngstadaas, Ståle Petter; Ellingsen, Jan Eirik & Haugen, Håvard Jostein (2024). Decontamination dental implant surfaces using a dental pellicle mode. Full text in Research Archive
• Lauretis, Angela De; Hussain, Badra; Ellingsen, Jan Eirik; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2024). A comparative evaluation of chemical decontamination products on the cleanliness of dental implant surfaces using a dental pellicle model. Full text in Research Archive
• Hussain, Badra; Lyngstadaas, Ståle Petter; Ellingsen, Jan Eirik & Haugen, Håvard Jostein (2024). A Comparative Investigation Of Chemical Decontamination Methods For In Situ Cleaning Of Dental Implant Surfaces. Full text in Research Archive
• Hussain, Badra; Simm, Roger; Bueno, Jaime; Giannettou, Savvas; Naemi, Ali-Oddin & Lyngstadaas, Ståle Petter [Show all 7 contributors for this article] (2023). Chemical decontamination strategies for treatment of peri-implant disease. Full text in Research Archive
• Hussain, Badra; Simm, Roger; Lyngstadaas, Ståle Petter; Bueno, Jamie & Haugen, Håvard Jostein (2023). Chemical decontamination strategies for treatment of peri-implant disease: using an in vitro dental pellicle-, and a multispecies biofilm model. Full text in Research Archive
• Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter; Cabrer, Marta Monjo & Perale, Giuseppe (2021). XENO-HYBRID BONE GRAFT RELEASING MATRIX-DERIVED INTRINSICALLY DISORDERED PROTEINS PROMOTES OSTEOGENIC DIFFERENTIATION OF HMSCS. Full text in Research Archive
• Rahmati, Maryam; Frank, Matthias Johannes; Walter, Sebastian Martin; Monjo, Marta Cabrer; 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. Full text in Research Archive
• Schweikle, Manuel; Bjørnøy, Sindre Hove; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein; Helvoort, Antonius Van & Sikorski, Pawel [Show all 7 contributors for this article] (2018). Self-mineralising synthetic injectable hydrogels for bone repair. Full text in Research Archive
• Villa, Oscar; Wohlfahrt, Johan Caspar; Mdala, Ibrahimu; Petzold, Christiane; Reseland, Janne Elin & Snead, Malcolm L. [Show all 7 contributors for this article] (2015). Proline-rich peptides accelerate oral mucosal wound healing. Full text in Research Archive
• 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. 29, p. 32–32. Full text in Research Archive
• 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), p. 459–462. Full text in Research Archive
• Geissler, Sebastian; Frank, Matthias Johannes; Walter, Martin Sebastian; Tiainen, Hanna; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2014). Coating of metal implant materials with strontium. Full text in Research Archive
• Walter, Martin Sebastian; Frank, Matthias Johannes; Satué, María; Monjo, Marta; Rønold, Hans Jacob & Lyngstadaas, Ståle Petter [Show all 7 contributors for this article] (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), p. 463–463. doi: 10.1016/j.dental.2014.01.015. Full text in Research Archive
• Wohlfahrt, Johan Caspar; Lyngstadaas, Ståle Petter; Aass, Anne Merete & Koldsland, Odd Carsten (2014). Implant Maintenance with a Chitosan Brush –A Randomized Clinical Trial. Full text in Research Archive
• Haugen, Håvard Jostein; Lyngstadaas, Ståle Petter & Vogt, Yngve (2014). Redder løse tenner og kreftskadde kjever. [Journal]. Apollon. Full text in Research Archive
• Haugen, Håvard Jostein & Lyngstadaas, Ståle Petter (2013). Like sterke som originalen. [Journal]. Den norske tannlegeforenings Tidende. Full text in Research Archive Show summary

  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. Full text in Research Archive
• Tiainen, Hanna; Wiedmer, David; Wohlfahrt, Johan Caspar; Lyngstadaas, Ståle Petter & Haugen, Håvard Jostein (2013). Highly porous ceramic titanium dioxide scaffolds for bone repair. Full text in Research Archive
• 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. Full text in Research Archive
• 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. Full text in Research Archive Show summary

  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.

• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein & Reseland, Janne Elin [Show all 7 contributors for this article] (2013). Local delivery of simvastatin on titanium dioxide scaffolds; a tissue engineering model. Full text in Research Archive
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein & Reseland, Janne Elin [Show all 7 contributors for this article] (2013). Coating titanium dioxide scaffold with simvastatin in alginate promote osteoblast differentiation in vitro. Full text in Research Archive
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein & Reseland, Janne Elin [Show all 7 contributors for this article] (2013). Enhanced in vitro bone differentiation on TiO₂ scaffold coated with simvastatin. Full text in Research Archive
• Pullisaar, Helen; Tiainen, Hanna; Landin, Maria Augusta Dos S Silva; Lyngstadaas, Ståle Petter; Haugen, Håvard Jostein & Reseland, Janne Elin [Show all 7 contributors for this article] (2013). Local delivery of simvastatin enhances bone differentiation on porous titanium dioxide scaffold. Full text in Research Archive

View all works in NVA